WO2014165727A1 - Traitement antimicrobien de surfaces de dispositif médical - Google Patents

Traitement antimicrobien de surfaces de dispositif médical Download PDF

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Publication number
WO2014165727A1
WO2014165727A1 PCT/US2014/032919 US2014032919W WO2014165727A1 WO 2014165727 A1 WO2014165727 A1 WO 2014165727A1 US 2014032919 W US2014032919 W US 2014032919W WO 2014165727 A1 WO2014165727 A1 WO 2014165727A1
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WO
WIPO (PCT)
Prior art keywords
coating
vessel
contact surface
catheter
plasma
Prior art date
Application number
PCT/US2014/032919
Other languages
English (en)
Inventor
Robert S. Abrams
Original Assignee
Sio2 Medical Products, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sio2 Medical Products, Inc. filed Critical Sio2 Medical Products, Inc.
Publication of WO2014165727A1 publication Critical patent/WO2014165727A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L9/00—Disinfection, sterilisation or deodorisation of air
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00889—Material properties antimicrobial, disinfectant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/10—Materials for lubricating medical devices

Definitions

  • the invention concerns an improved medical device comprising: a surface which is configured to contact a human or animal fluid or tissue or a pharmaceutical preparation; and silver ions or other antimicrobial material coated in or incorporated on the surface in an amount effective to inhibit microbial growth on or adjacent to the surface.
  • Nosocomial, or hospital-related bacterial infections are estimated to be the fifth- leading cause of death in the United States, after heart disease, cancer, stroke, and pneumonia or flu.
  • the Centers for Disease Control estimate that nosocomial infections cost hospitals more than $2300 per patient for diagnosis and treatment. Many instances, such as vascular catheter infection, can cost $25,000 per episode. Overall, the infections cost hospitals $4.8 billion annually in extended care and treatment.
  • Silver is effective across a broad range of bacteria and against mutating pathogens. It is also effective in blocking fungi and yeasts known to cause disease.
  • silver 70-88 ⁇ g of silver each day.
  • Other heavy metals such as mercury and lead, can bond chemically and accumulate in the body, which can inhibit metabolism.
  • silver is, for the most part, nontoxic. Cases of extreme exposure have caused upper respiratory or mild eye irritation, and prolonged exposure can cause argyria.
  • silver oxide is an effective antimicrobial at levels as little as 1 ppm, so toxicity concerns are mostly irrelevant.
  • U.S. Published Patent Application 2006-0198903 Al states that it relates to "efficient methods for depositing highly adherent anti-microbial materials onto a wide range of surfaces. A controlled cathodic arc process is described, which results in enhanced adhesion of silver oxide to polymers and other surfaces, such as surfaces of medical devices. Deposition of anti-microbial materials directly onto the contact surfaces is possible in a cost- effective manner that maintains high anti-microbial activity over several weeks when the coated devices are employed in vivo.” This application is hereby incorporated by reference in its entirety here. See also PCT Published Application WO03044240A1.
  • Storey et al. also identifies several alternative metals for antimicrobial use: gold, platinum, copper, tantalum, titanium, zirconium, hafnium, and zinc.
  • Storey et al. identifies a metal or polymeric surface as potential contact surfaces for antimicrobial treatment, and states that "the Ag/AgO impregnates the metal contact surface up to a depth of about 10 nanometers," and a polymeric contact surface "up to a depth of about 100 nanometers.”
  • Exemplary polymeric contact surfaces identified are: "polypropylene, polyurethane, EPTFE, PTFE, polyimide, polyester, PEEK, UHMWPE, and nylon.”
  • Biofilm formation is extremely difficult to eliminate once it has begun. Preventing biofilms on medical devices and implants is key to controlling their contribution to establishing infection. Because biofilm formation is dependent upon a surface, one strategy is to modify the surface to make it hostile to microorganisms. Ionic silver is becoming a favored substance for surface modification for a number of reasons, including the following: [0014] "It has broad-spectrum antimicrobial action.
  • IPD Ionic Plasma Deposition
  • An aspect of the present invention is a method of making an antimicrobial medical device.
  • a medical device or material or portion thereof comprising a contact surface.
  • a first treatment of SiOx, SiOxCy, or SiNxCy is applied to the contact surface.
  • a second antimicrobially effective treatment is applied to the contact surface.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • FIG. 1 is a schematic diagram showing a vessel processing system according to an embodiment of the disclosure.
  • FIG. 2 is a schematic sectional view of a vessel holder in a coating station according to an embodiment of the disclosure.
  • FIG. 3 is a view similar to FIG. 2 of an alternative embodiment of the disclosure.
  • FIG. 4 is a diagrammatic plan view of an alternative embodiment of the vessel holder.
  • FIG. 5 is a diagrammatic plan view of another alternative embodiment of the vessel holder.
  • FIG. 6 is a view similar to FIG. 2 of vessel inspection apparatus.
  • FIG. 7 is a view similar to FIG. 2 of alternative vessel inspection apparatus.
  • FIG. 8 is a section taken along section lines A— A of FIG. 2.
  • FIG. 9 is an alternative embodiment of the structure shown in FIG. 8.
  • FIG. 10 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a CCD detector.
  • FIG. 11 is a detail view similar to FIG. 10 of a light source and detector that are reversed compared to the corresponding parts of FIG. 6.
  • FIG. 12 is a view similar to FIG. 2 of a vessel holder in a coating station according to still another embodiment of the disclosure, employing microwave energy to generate the plasma.
  • FIG. 13 is a view similar to FIG. 2 of a vessel holder in a coating station according to yet another embodiment of the disclosure, in which the vessel can be seated on the vessel holder at the process station.
  • FIG. 14 is a view similar to FIG. 2 of a vessel holder in a coating station according to even another embodiment of the disclosure, in which the electrode can be configured as a coil.
  • FIG. 15 is a view similar to FIG. 2 of a vessel holder in a coating station according to another embodiment of the disclosure, employing a tube transport to move a vessel to and from the coating station.
  • FIG. 16 is a diagrammatic view of the operation of a vessel transport system, such as the one shown in FIG. 15, to place and hold a vessel in a process station.
  • FIG. 17 is a diagrammatic view of a mold and mold cavity for forming a vessel according to an aspect of the present disclosure.
  • FIG. 18 is a diagrammatic view of the mold cavity of FIG. 17 provided with a vessel coating device according to an aspect of the present disclosure.
  • FIG. 19 is a view similar to FIG. 17 provided with an alternative vessel coating device according to an aspect of the present disclosure.
  • FIG. 20 is an exploded longitudinal sectional view of a syringe and cap adapted for use as a prefilled syringe.
  • FIG. 21 is a view generally similar to FIG. 2 showing a capped syringe barrel and vessel holder in a coating station according to an embodiment of the disclosure.
  • FIG. 22 is a view generally similar to FIG. 21 showing an uncapped syringe barrel and vessel holder in a coating station according to yet another embodiment of the invention.
  • FIG. 23 is a perspective view of a blood collection tube assembly having a closure according to still another embodiment of the invention.
  • FIG. 24 is a fragmentary section of the blood collection tube and closure assembly of FIG. 23.
  • FIG. 25 is an isolated section of an elastomeric insert of the closure of FIGS. 23 and 24.
  • FIG. 26 is a view similar to FIG. 22 of another embodiment of the invention for processing syringe barrels and other vessels.
  • FIG. 27 is an enlarged detail view of the processing vessel of FIG. 26.
  • FIG. 28 is a schematic view of an alternative processing vessel.
  • FIG. 29 is a schematic view showing outgassing of a material through a coating.
  • FIG. 30 is a schematic sectional view of a test set-up for causing outgassing of the wall of a vessel to the interior of the vessel and measurement of the outgassing using a measurement cell interposed between the vessel and a source of vacuum.
  • FIG. 31 is a plot of outgassing mass flow rate measured on the test-set-up of FIG. 30 for multiple vessels.
  • FIG. 32 is a bar graph showing a statistical analysis of the endpoint data shown in FIG. 31.
  • FIG. 33 is a longitudinal section of a combined syringe barrel and gas receiving volume according to another embodiment of the invention.
  • FIG. 34 is a view similar to FIG 34 of another embodiment of the invention including an electrode extension.
  • FIG. 35 is a view taken from section lines 35 - 35 of FIG. 34, showing the distal gas supply openings and extension electrode of FIG. 34.
  • FIG. 36 is a perspective view of a double-walled blood collection tube assembly according to still another embodiment of the invention.
  • FIG. 37 is a view similar to FIG. 22 showing another embodiment.
  • FIG. 38 is a view similar to FIG. 22 showing still another embodiment.
  • FIG. 39 is a view similar to FIG. 22 showing yet another embodiment.
  • FIG. 40 is a view similar to FIG. 22 showing even another embodiment.
  • FIG. 41 is a plan view of the embodiment of FIG. 40.
  • FIG. 42 is a fragmentary detail longitudinal section of an alternative sealing arrangement, usable for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12- 16, 18, 19, 33, and 37-41 for seating a vessel on a vessel holder.
  • FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 2, 3, 6-10, 12-22, 26-28, 33- 34, and 37-41.
  • FIG. 43 is a further enlarged detail view of the sealing arrangement shown in FIG. 42.
  • FIG. 44 is a view similar to FIG. 2 of an alternative gas delivery tube/inner electrode usable, for example with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 33, 37-43, 46-49, and 52-54.
  • FIG. 45 is an alternative construction for a vessel holder usable, for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16, 18, 19, 21, 22, 26, 28, 33-35, and 37-44.
  • FIG. 46 is a schematic sectional view of an array of gas delivery tubes and a mechanism for inserting and removing the gas delivery tubes from a vessel holder, showing a gas delivery tube in its fully advanced position.
  • FIG. 47 is a view similar to FIG. 46, showing a gas delivery tube in an intermediate position.
  • FIG. 48 is a view similar to FIG. 46, showing a gas delivery tube in a retracted position.
  • the array of gas delivery tubes of FIGS. 46-48 are usable, for example, with the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54.
  • the mechanism of FIGS. 46-48 is usable, for example, with the gas delivery tube embodiments of FIGS. 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54, as well as with the probes of the vessel inspection apparatus of FIGS. 6 and 7.
  • FIG. 49 is a view similar to FIG. 16 showing a mechanism for delivering vessels to be treated and a cleaning reactor to a PECVD coating apparatus.
  • the mechanism of FIG. 49 is usable with the vessel inspection apparatus of FIGS. 1, 9, 15, and 16, for example.
  • FIG. 50 is an exploded view of a two-piece syringe barrel and Luer lock fitting.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
  • FIG. 51 is an assembled view of the two-piece syringe barrel and Luer lock fitting of FIG. 50.
  • FIG. 52 is a view similar to FIG. 42 showing a syringe barrel being treated that has no flange or finger stops 440.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
  • FIG. 53 is a schematic view of an assembly for treating vessels. The assembly is usable with the apparatus of FIGS. 1-3, 8-9, 12-16, 18-22, 26-28, 33-35, and 37-49.
  • FIG. 54 is a diagrammatic view of the embodiment of FIG. 53.
  • FIG. 55 is a diagrammatic view similar to FIG. 2 of an embodiment of the invention including a plasma screen.
  • FIG. 56 is a schematic sectional view of an array of gas delivery tubes, having independent gas supplies and a mechanism for inserting and removing the gas delivery tubes from a vessel holder.
  • FIG. 57 is a plot of outgassing mass flow rate measured in Example 19.
  • FIG. 58 shows a linear rack, otherwise similar to FIG. 4.
  • FIG. 59 shows a schematic representation of a vessel processing system according to an exemplary embodiment of the present invention.
  • FIG. 60 shows a schematic representation of a vessel processing system according to another exemplary embodiment of the present invention.
  • FIG. 61 shows a processing station of a vessel processing system according to an exemplary embodiment of the present invention.
  • FIG. 62 shows a portable vessel holder according to an exemplary embodiment of the present invention.
  • Vessel processing system 94 Vacuum duct
  • Optical source transmission 112 Vessel holder (Fig. 3) station (defects) 114 Housing (of 50 or 112)
  • Vessel holder Exterior contact surface of
  • Vessel holder 120 Vessel holder (array)
  • Vessel holder 122 Vessel port (Fig. 4, 58)
  • Vessel holder 142 PECVD gas inlet port
  • Vacuum line (to 98)
  • Vessel holder 150 Flexible line (of 134)
  • RF radio frequency
  • First and “second” or similar references to, e.g., processing stations or processing devices refer to the minimum number of processing stations or devices that are present, but do not necessarily represent the order or total number of processing stations and devices. These terms do not limit the number of processing stations or the particular processing carried out at the respective stations.
  • an "organosilicon precursor” is a compound having at least one of the linkage:
  • a volatile organosilicon precursor defined as such a precursor that can be supplied as a vapor in a PECVD apparatus, is an optional organosilicon precursor.
  • the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors.
  • the invention has particular application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel.
  • a “vessel” in the context of the present invention can be any type of article that is adapted to contain or convey a material.
  • the material can be a liquid, a gas, a solid, or any two or more of these.
  • One example of a vessel is an article with at least one opening and a wall defining an interior contact surface.
  • at least a portion of the interior contact surface defines a "contact surface” which is treated according to the present disclosure.
  • the term “at least” in the context of the present invention means "equal or more" than the integer following the term.
  • a vessel in the context of the present invention has one or more openings.
  • One or two openings like the openings of a sample tube (one opening) or a syringe barrel (two openings) are preferred. If the vessel has two or more openings, they can be of same or different size. If there is more than one opening, one opening can be used for the gas inlet for a PECVD coating method according to the present invention, while the other openings are either capped or open.
  • a vessel according to the present invention can be a sample tube, e.g. for collecting or storing biological fluids like blood or urine, a syringe (or a part thereof, for example a syringe barrel) for storing or delivering a biologically active compound or composition, e.g. a medicament or pharmaceutical composition, a vial or ampoule for storing biological materials or biologically active compounds or compositions, a pipe, e.g. a catheter for transporting biological materials or biologically active compounds or compositions, or a cuvette for holding fluids, e.g. for holding biological materials or biologically active compounds or compositions.
  • a vessel can be of any shape.
  • a vessel has a substantially cylindrical wall adjacent to at least one of its open ends.
  • the interior wall of a vessel of this type is cylindrically shaped, like, e.g. in a sample tube or a syringe barrel.
  • Sample tubes and syringes or their parts for example syringe barrels
  • vials for example syringe barrels
  • petri dishes which commonly are generally cylindrical, are contemplated.
  • contemplated vessels include well or non- well slides or plates, for example titer plates or microtiter plates.
  • Still other non-limiting examples of contemplated vessels include pump contact surfaces in contact with the pumped material, including impeller contact surfaces, pump chamber contact surfaces and the like.
  • Even other non-limiting examples of contemplated vessels include parts of an fluid containment, pumping, processing, filtering, and delivery system, such as an intravenous fluid delivery system, a blood processing system (such as a heart-lung machine or a blood component separator) a dialysis system, or the body or insulin contacting surfaces of an insulin delivery system, as several examples.
  • vessels examples include tubing, pump interior contact surfaces, drug or saline containing bags or bottles, adapters and tubing connectors for connecting parts of the system together, intravenous needles and needle assemblies, membranes and filters, etc.
  • Other examples of vessels include measuring and delivery devices such as pipettes.
  • the invention has more general application to "contact surfaces" of medical devices and the like used or usable in contact with human or animal fluids or tissues, whether or not associated with a vessel.
  • Some additional non-limiting examples of devices having contact surfaces are devices inserted in an orifice, through the skin, or otherwise within the body of a human or animal, such as thermometers, probes, guide wires, catheters, electrical leads, surgical drains, pacemakers, defibrillators, stents, contact lenses, artificial lens replacements, corneal replacements, and other devices placed in contact with the eye, orthopedic devices such as screws, plates, and rods, clothing, face masks, eye shields, and other equipment worn by medical personnel, surgical drapes, sheet or fabric material used to make the same, surgical instruments such as saws and saw blades, drills and drill bits, etc.
  • the invention further has application to any contact surfaces of devices used or usable in contact with pharmaceutical preparations or other materials, such as ampoules, vials, syringes, bottles, bags, or other containment vessels, stirring rods, impellers, stirring pellets, etc., also within the definition of "contact surfaces.”
  • an ACL/PCL Reconstruction System an adapter, an adhesion barrier, an agar petri dish, an anesthesia unit, an anesthesia ventilator, an angiographic catheter, an ankle replacement, an aortic valve replacement, an apnea monitor, an applicator, an argon enhanced coagulation unit, an artificial facet replacement, an artificial heart, an artificial heart valve, an artificial organ, an artificial pacemaker, an artificial pancreas, an artificial urinary bladder, an aspirator, an atherectomy catheter, an auditory brainstem implant, an auto transfusion unit, a bag, a balloon catheter, a bare-metal stent, a beaker a bileaflet valve, a biliary stent, a bio implant, a bioceramic device, a bioresorbable stent, a biphasic cuirass ventilation, a blood culture device
  • implantable birth control device an O'Neil aspirating and irrigating needle, an O'Neil balloon infuser, an O'Neil intermittent urinary catheter, a contact lens, an orthopedic implant, an osseointegration implant, an oxinium replacement joint material, a pacemaker, a pacing Catheter, a pain management pump, a palatal obturator, a pancreatic Stent, a penile prosthesis, a penis enlargement device, a peripheral stent, a Peripherally Inserted Central Catheter (PICC), a peristaltic pump, a peritoneovenous shunt, a petri dish, a phonocardiograph, a phototherapy unit, a Pipette, a polyaxial screw, a port (medical), a portacaval shunt, a positive airway pressure device, a prepared media device, a pressure accessory or cable, a pressure transducer, a prostatic catheter, a
  • a “hydrophobic layer” in the context of the present invention means that the coating lowers the wetting tension of a surface coated with the coating, compared to the corresponding uncoated surface. Hydrophobicity is thus a function of both the uncoated substrate and the coating. The same applies with appropriate alterations for other contexts wherein the term “hydrophobic” is used.
  • the term “hydrophilic” means the opposite, i.e. that the wetting tension is increased compared to reference sample.
  • the present hydrophobic layers are primarily defined by their hydrophobicity and the process conditions providing hydrophobicity, and optionally can have a composition according to the empirical composition or sum formula SiwOxCyHz, for example where w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9, optionally where w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from 6 to about 9.
  • These values of w, x, y, and z are applicable to the empirical composition SiwOxCyHz throughout this specification.
  • the values of w, x, y, and z used throughout this specification should be understood as ratios or an empirical formula (e.g.
  • octamethylcyclotetrasiloxane which has the molecular composition Si404C8H24, can be described by the following empirical formula, arrived at by dividing each of w, x, y, and z in the molecular formula by 4, the largest common factor: Sil01C2H6.
  • the values of w, x, y, and z are also not limited to integers.
  • (acyclic) octamethyltrisiloxane, molecular composition S1 3 O 2 C 8 H 24 is reducible to SiiO 0 .67C2.67Hg.
  • wetting tension is a specific measure for the hydrophobicity or hydrophilicity of a surface.
  • An optional wetting tension measurement method in the context of the present invention is ASTM D 2578 or a modification of the method described in ASTM D 2578. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film surface for exactly two seconds. This is the film's wetting tension.
  • the procedure utilized is varied herein from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with
  • a “lubricity layer” according to the present invention is a coating which has a lower frictional resistance than the uncoated surface. In other words, it reduces the frictional resistance of the coated surface in comparison to a reference surface which is uncoated.
  • the present lubricity layers are primarily defined by their lower frictional resistance than the uncoated surface and the process conditions providing lower frictional resistance than the uncoated surface, and optionally can have a composition according to the empirical composition SiwOxCyHz, as defined in this Definition Section. "Frictional resistance” can be static frictional resistance and/or kinetic frictional resistance.
  • One of the optional embodiments of the present invention is a syringe part, e.g.
  • the relevant static frictional resistance in the context of the present invention is the breakout force as defined herein
  • the relevant kinetic frictional resistance in the context of the present invention is the plunger sliding force as defined herein.
  • the plunger sliding force as defined and determined herein is suitable to determine the presence or absence and the lubricity characteristics of a lubricity layer in the context of the present invention whenever the coating is applied to any syringe or syringe part, for example to the inner wall of a syringe barrel.
  • the breakout force is of particular relevance for evaluation of the coating effect on a prefilled syringe, i.e. a syringe which is filled after coating and can be stored for some time, e.g. several months or even years, before the plunger is moved again (has to be "broken out").
  • the "plunger sliding force” in the context of the present invention is the force required to maintain movement of a plunger in a syringe barrel, e.g. during aspiration or dispense. It can advantageously be determined using the ISO 7886-1: 1993 test described herein and known in the art. A synonym for "plunger sliding force” often used in the art is “plunger force” or “pushing force”.
  • the "breakout force” in the context of the present invention is the initial force required to move the plunger in a syringe, for example in a prefilled syringe.
  • An "antimicrobially effective" treatment means that the treated surface has greater antimicrobial activity, measured by a recognized test method, than a control represented by the same surface that has not been antimicrobially treated.
  • a medical device or material or portion thereof comprising a contact surface.
  • a first treatment of SiO x , SiO x C y , or SiN x C y is applied to the contact surface.
  • a second, antimicrobially effective, treatment is applied to the contact surface with its first treatment.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • the contact surface is defined in the definitions section above.
  • the precursor for the PECVD coating of the present invention is broadly defined as an organometallic precursor.
  • An organometallic precursor is defined in this specification as comprehending compounds of metal elements from Group III and/or Group IV of the Periodic Table having organic residues, e.g. hydrocarbon, aminocarbon or oxycarbon residues.
  • Organometallic compounds as presently defined include any precursor having organic moieties bonded to silicon or other Group III/ IV metal atoms directly, or optionally bonded through oxygen or nitrogen atoms.
  • the relevant elements of Group III of the Periodic Table are Boron, Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum, Aluminum and Boron being preferred.
  • the relevant elements of Group IV of the Periodic Table are Silicon, Germanium, Tin, Lead, Titanium, Zirconium, Hafnium, and Thorium, with Silicon and Tin being preferred. Other volatile organic compounds can also be contemplated. However, organosilicon compounds are preferred for performing present invention.
  • organosilicon precursor is contemplated, where an "organosilicon precursor" is defined throughout this specification most broadly as a compound having at least one of the linkages:
  • the first structure immediately above is a tetravalent silicon atom connected to an oxygen atom and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom).
  • the second structure immediately above is a tetravalent silicon atom connected to an -NH- linkage and an organic carbon atom (an organic carbon atom being a carbon atom bonded to at least one hydrogen atom).
  • the organosilicon precursor is selected from the group consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, and a combination of any two or more of these precursors. Also,
  • an oxygen-containing precursor e.g. a siloxane
  • a representative predicted empirical composition resulting from PECVD under conditions forming a hydrophobic or lubricating coating would be Si w O x C y H z as defined in the Definition Section, while a representative predicted empirical composition resulting from PECVD under conditions forming a barrier coating would be SiO x , where x in this formula is from about 1.5 to about 2.9.
  • a nitrogen- containing precursor e.g. a silazane
  • the predicted composition would be Si w* N x* C y* H z* , i.e.
  • Si w O x C y H z as specified in the Definition Section, O is replaced by N and the indices are adapted to the higher valency of N as compared to O (3 instead of 2).
  • the latter adaptation will generally follow the ratio of w, x, y and z in a siloxane to the corresponding indices in its aza counterpart.
  • Si w* N x* C y* H z* in which w*, x*, y*, and z* are defined the same as w, x, y, and z for the siloxane counterparts, but for an optional deviation in the number of hydrogen atoms.
  • One type of precursor starting material having the above empirical formula is a linear siloxane, for example a material having the following formula:
  • each R is independently selected from alkyl, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others, and n is 1, 2, 3, 4, or greater, optionally two or greater.
  • alkyl for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others
  • n is 1, 2, 3, 4, or greater, optionally two or greater.
  • HMDSO hexamethyldisiloxane
  • decamethyltetrasilazane or combinations of two or more of these.
  • V.C. Another type of precursor starting material is a monocyclic siloxane, for example a material having the following structural formula:
  • R is defined as for the linear structure and "a" is from 3 to about 10, or the analogous monocyclic silazanes.
  • a is from 3 to about 10
  • contemplated hetero-substituted and unsubstituted monocyclic siloxanes and silazanes include
  • V.C. Another type of precursor starting material is a polycyclic siloxane, for example a material having one of the following structural formulas:
  • Y can be oxygen or nitrogen
  • E is silicon
  • Z is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • Y oxygen
  • the respective structures from left to right, are a silatrane, a silquasilatrane, and a silproatrane.
  • Y is nitrogen
  • the respective structures are an azasilatrane, an azasilquasiatrane, and an azasilproatrane.
  • V.C. Another type of polycyclic siloxane precursor starting material is a
  • each R is a hydrogen atom or an organic substituent, for example alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.
  • SST-eMOl poly(methylsilsesquioxane) in which each R is methyl
  • SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane) in which 90% of the R groups are methyl, 10% are hydrogen atoms. This material is available in a 10% solution in tetrahydrofuran, for example. Combinations of two or more of these are also contemplated.
  • a contemplated precursor examples include methylsilatrane, CAS No. 2288-13-3, in which each Y is oxygen and Z is methyl, methylazasilatrane, SST-eMOl poly(methylsilsesquioxane), in which each R optionally can be methyl, SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are methyl and 10% are hydrogen atoms, or a combination of any two or more of these.
  • V.C The analogous polysilsesquiazanes in which -NH- is substituted for the oxygen atom in the above structure are also useful for making analogous coatings.
  • contemplated polysilsesquiazanes are a poly(methylsilsesquiazane), in which each R is methyl, and a poly(Methyl-Hydridosilsesquiazane, in which 90% of the R groups are methyl, 10% are hydrogen atoms. Combinations of two or more of these are also contemplated.
  • V.C One particularly contemplated precursor for the lubricity layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
  • One particularly contemplated precursor for the hydrophobic layer according to the present invention is a monocyclic siloxane, for example is octamethylcyclotetrasiloxane.
  • One particularly contemplated precursor for the barrier coating according to the present invention is a linear siloxane, for example is HMDSO.
  • the applying step optionally can be carried out by vaporizing the precursor and providing it in the vicinity of the substrate.
  • OMCTS is usually vaporized by heating it to about 50°C before applying it to the PECVD apparatus.
  • PECVD method In the context of the present invention, the following PECVD method is generally applied, which contains the following steps:
  • the coating characteristics are advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • the coating is advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • the coating characteristics are advantageously set by one or more of the following conditions: the plasma properties, the pressure under which the plasma is applied, the power applied to generate the plasma, the presence and relative amount of 0 2 in the gaseous reactant, the plasma volume, and the organosilicon precursor.
  • characteristics are set by the presence and relative amount of 0 2 in the gaseous reactant and/or the power applied to generate the plasma.
  • the plasma is in an optional aspect a non- hollow-cathode plasma.
  • the plasma is generated at reduced pressure (as compared to the ambient or atmospheric pressure).
  • the reduced pressure is less than 300 mTorr, optionally less than 200 mTorr, even optionally less than 100 mTorr.
  • the PECVD optionally is performed by energizing the gaseous reactant containing the precursor with electrodes powered at a frequency at microwave or radio frequency, and optionally at a radio frequency.
  • the radio frequency preferred to perform an embodiment of the invention will also be addressed as "RF frequency".
  • a typical radio frequency range for performing the present invention is a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz.
  • a frequency of 13.56 MHz is most preferred, this being a government sanctioned frequency for conducting PECVD work.
  • RF operates a lower power, there is less heating of the substrate/vessel. Because the focus of the present invention is putting a plasma coating on plastic substrates, lower processing temperature are desired to prevent melting/distortion of the substrate.
  • the microwave PECVD is applied in short bursts, by pulsing the power. The power pulsing extends the cycle time for the coating, which is undesired in the present invention.
  • the higher frequency microwave can also cause offgassing of volatile substances like residual water, oligomers and other materials in the plastic substrate. This offgassing can interfere with the PECVD coating.
  • a major concern with using microwave for PECVD is delamination of the coating from the substrate. Delamination occurs because the microwaves change the contact surface of the substrate prior to depositing the coating layer.
  • interface coating layers have been developed for microwave PECVD to achieve good bonding between the coating and the substrate. No such interface coating layer is needed with RF PECVD as there is no risk of delamination.
  • the lubricity layer and hydrophobic layer according to the present invention are advantageously applied using lower power. RF power operates at lower power and provides more control over the PECVD process than microwave power. Nonetheless, microwave power, though less preferred, is usable under suitable process conditions.
  • the lumen is the lumen of a vessel coated according to the present invention.
  • the RF power should scale with the volume of the vessel if the same electrode system is employed.
  • the power which has to be applied in order to achieve the same or a similar coating in a vessel of same geometry, but different size can easily be found.
  • the influence of the vessel geometry on the power to be applied is illustrated by the results of the Examples for tubes in comparison to the Examples for syringe barrels.
  • the plasma is generated with electrodes powered with sufficient power to form a coating on the substrate contact surface.
  • the plasma is optionally generated
  • the plasma is optionally generated (i) with electrodes supplied with an electric power of from 8 to 500 W, optionally from 20 to 400 W, optionally from 35 to 350 W, even optionally from 44 to 300 W, optionally from 44 to 70 W; and/or
  • the ratio of the electrode power to the plasma volume is equal or more than 5 W/ml, optionally is from 6 W/ml to 150 W/ml, optionally is from 7 W/ml to 100 W/ml, optionally from 7 W/ml to 20 W/ml.
  • the vessel geometry can also influence the choice of the gas inlet used for the PECVD coating.
  • a syringe can be coated with an open tube inlet, and a tube can be coated with a gas inlet having small holes which is extended into the tube.
  • the power (in Watts) used for PECVD also has an influence on the coating properties.
  • an increase of the power will increase the barrier properties of the coating, and a decrease of the power will increase the lubricity and hydrophobicity of the coating.
  • a power of less than 30 W will lead to a coating which is predominantly a barrier coating, while a power of more than 30 W will lead to a coating which is predominantly a lubricity layer (see Examples).
  • a further parameter determining the coating properties is the ratio of 0 2 (or another oxidizing agent) to the precursor (e.g. organosilicon precursor) in the gaseous reactant used for generating the plasma.
  • 0 2 or another oxidizing agent
  • the precursor e.g. organosilicon precursor
  • an increase of the 0 2 ratio in the gaseous reactant will increase the barrier properties of the coating, and a decrease of the 0 2 ratio will increase the lubricity and hydrophobicity of the coating.
  • 0 2 is optionally present in a volume-volume ratio to the gaseous reactant of from 0: 1 to 5: 1, optionally from 0: 1 to 1: 1, even optionally from 0: 1 to 0.5: 1 or even from 0: 1 to 0.1: 1.
  • the gaseous reactant should comprise less than 1 vol 0 2 , for example less than 0.5 vol 0 2 , and optionally is 0 2 -free. The same applies to a hydrophobic layer.
  • the 0 2 is optionally present in a volume : volume ratio to the gaseous reactant of from 1 : 1 to 100 : 1 in relation to the silicon containing precursor, optionally in a ratio of from 5 : 1 to 30 : 1, optionally in a ratio of from 10 : 1 to 20 : 1, even optionally in a ratio of 15 : 1.
  • V.A A specific embodiment is a method of applying a barrier coating of SiO x , defined in this specification (unless otherwise specified in a particular instance) as a coating containing silicon, oxygen, and optionally other elements, in which x, the ratio of oxygen to silicon atoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. These alternative definitions of x apply to any use of the term SiO x in this specification.
  • the barrier coating is applied to a contact surface, for example a sample collection tube, a syringe barrel, or another type of vessel. The method includes several steps.
  • V.A A vessel wall is provided, as is a reaction mixture comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas.
  • plasma forming gas i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas.
  • V.A. Plasma is formed in the reaction mixture that is substantially free of hollow cathode plasma.
  • the vessel wall is contacted with the reaction mixture, and the coating of SiO x is deposited on at least a portion of the vessel wall.
  • V.A the generation of a uniform plasma throughout the portion of the vessel to be coated is contemplated, as it has been found in certain instances to generate an SiO x coating providing a better barrier against oxygen.
  • Uniform plasma means regular plasma that does not include a substantial amount of hollow cathode plasma (which has a higher emission intensity than regular plasma and is manifested as a localized area of higher intensity interrupting the more uniform intensity of the regular plasma).
  • V.A The hollow cathode effect is generated by a pair of conductive contact surfaces opposing each other with the same negative potential with respect to a common anode. If the spacing is made (depending on the pressure and gas type) such that the space charge sheaths overlap, electrons start to oscillate between the reflecting potentials of the opposite wall sheaths leading to multiple collisions as the electrons are accelerated by the potential gradient across the sheath region. The electrons are confined in the space charge sheath overlap which results in very high ionization and high ion density plasmas. This phenomenon is described as the hollow cathode effect. Those skilled in the art are able to vary the processing conditions, such as the power level and the feed rates or pressure of the gases, to form uniform plasma throughout or to form plasma including various degrees of hollow cathode plasma.
  • microwave energy can be used to generate the plasma in a PECVD process.
  • the processing conditions can be different, however, as microwave energy applied to a thermoplastic vessel will excite (vibrate) water molecules. Since there is a small amount of water in all plastic materials, the microwaves will heat the plastic. As the plastic heats, the large driving force created by the vacuum inside of the device relative to atmospheric pressure outside the device will pull free or easily desorb materials to the interior contact surface 88 where they will either become volatile or will be weakly bound to the contact surface. The weakly bound materials will then create an interface that can hinder subsequent coatings (deposited from the plasma) from adhering to the plastic interior contact surface 88 of the device.
  • V.A As one way to negate this coating hindering effect, a coating can be deposited at very low power (in the example above 5 to 20 Watts at 2.45 GHz) creating a cap onto which subsequent coatings can adhere. This results in a two-step coating process (and two coating layers).
  • the initial gas flows for the capping layer
  • the capping layer can be changed to 2 seem ("standard cubic centimeters per minute") HMDSO and 20 seem oxygen with a process power of 5 to 20 Watts for approximately 2-10 seconds.
  • the gases can be adjusted to the flows in the example above and the power level increased to 20-50 Watts so that an SiO x coating, in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, can be deposited.
  • the capping layer might provide little to no functionality in certain embodiments, except to stop materials from migrating to the vessel interior contact surface 88 during the higher power SiO x coating deposition.
  • migration of easily desorbed materials in the device walls typically is not an issue at lower frequencies such as most of the RF range, since the lower frequencies do not excite (vibrate) molecular species.
  • the vessel 80 can be dried to remove embedded water before applying microwave energy. Desiccation or drying of the vessel 80 can be accomplished, for example, by thermally heating the vessel 80, as by using an electric heater or forced air heating. Desiccation or drying of the vessel 80 also can be accomplished by exposing the interior of the vessel 80, or gas contacting the interior of the vessel 80, to a desiccant. Other expedients for drying the vessel, such as vacuum drying, can also be used. These expedients can be carried out in one or more of the stations or devices illustrated or by a separate station or device.
  • V.A the coating hindering effect described above can be addressed by selection or processing of the resin from which the vessels 80 are molded to minimize the water content of the resin.
  • FIGS. 26 and 27 show a method and apparatus generally indicated at 290 for coating an inner contact surface 292 of a restricted opening 294 of a generally tubular vessel 250 to be processed, for example the restricted front opening 294 of a syringe barrel 250, by PECVD.
  • the previously described process is modified by connecting the restricted opening 294 to a processing vessel 296 and optionally making certain other modifications.
  • the generally tubular vessel 250 to be processed includes an outer contact surface 298, an inner or interior contact surface 254 defining a lumen 300, a larger opening 302 having an inner diameter, and a restricted opening 294 that is defined by an inner contact surface 292 and has an inner diameter smaller than the inner diameter of the larger opening 302.
  • the processing vessel 296 has a lumen 304 and a processing vessel opening 306, which optionally is the only opening, although in other embodiments a second opening can be provided that optionally is closed off during processing.
  • the processing vessel opening 306 is connected with the restricted opening 294 of the vessel 250 to be processed to establish communication between the lumen 300 of the vessel 250 to be processed and the processing vessel lumen via the restricted opening 294.
  • V.B At least a partial vacuum is drawn within the lumen 300 of the vessel 250 to be processed and lumen 304 of the processing vessel 296.
  • a PECVD reactant is flowed from the gas source 144 (see FIG. 7) through the first opening 302, then through the lumen 300 of the vessel 250 to be processed, then through the restricted opening 294, then into the lumen 304 of the processing vessel 296.
  • the PECVD reactant can be introduced through the larger opening 302 of the vessel 250 by providing a generally tubular inner electrode 308 having an interior passage 310, a proximal end 312, a distal end 314, and a distal opening 316, in an alternative embodiment multiple distal openings can be provided adjacent to the distal end 314 and communicating with the interior passage 310.
  • the distal end of the electrode 308 can be placed adjacent to or into the larger opening 302 of the vessel 250 to be processed.
  • a reactant gas can be fed through the distal opening 316 of the electrode 308 into the lumen 300 of the vessel 250 to be processed.
  • the reactant will flow through the restricted opening 294, then into the lumen 304, to the extent the PECVD reactant is provided at a higher pressure than the vacuum initially drawn before introducing the PECVD reactant.
  • V.B. Plasma 318 is generated adjacent to the restricted opening 294 under conditions effective to deposit a coating of a PECVD reaction product on the inner contact surface 292 of the restricted opening 294.
  • the plasma is generated by feeding RF energy to the generally U-shaped outer electrode 160 and grounding the inner electrode 308.
  • the feed and ground connections to the electrodes could also be reversed, though this reversal can introduce complexity if the vessel 250 to be processed, and thus also the inner electrode 308, are moving through the U-shaped outer electrode while the plasma is being generated.
  • the plasma 318 generated in the vessel 250 during at least a portion of processing can include hollow cathode plasma generated inside the restricted opening 294 and/or the processing vessel lumen 304.
  • the generation of hollow cathode plasma 318 can contribute to the ability to successfully apply a barrier coating at the restricted opening 294, although the invention is not limited according to the accuracy or applicability of this theory of operation.
  • the processing can be carried out partially under conditions generating a uniform plasma throughout the vessel 250 and the gas inlet, and partially under conditions generating a hollow cathode plasma, for example adjacent to the restricted opening 294.
  • the process is desirably operated under such conditions, as explained here and shown in the drawings, that the plasma 318 extends substantially throughout the syringe lumen 300 and the restricted opening 294.
  • the plasma 318 also desirably extends substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296. This assumes that a uniform coating of the interior 254 of the vessel 250 is desired. In other embodiments non-uniform plasma can be desired.
  • the plasma 318 have a substantially uniform color throughout the syringe lumen 300 and the restricted opening 294 during processing, and optionally a substantially uniform color substantially throughout the syringe lumen 300, the restricted opening 294, and the lumen 304 of the processing vessel 296.
  • the plasma desirably is substantially stable throughout the syringe lumen 300 and the restricted opening 294, and optionally also throughout the lumen 304 of the processing vessel 296.
  • the restricted opening 294 has a first fitting 332 and the processing vessel opening 306 has a second fitting 334 adapted to seat to the first fitting 332 to establish communication between the lumen 304 of the processing vessel 296 and the lumen 300 of the vessel 250 to be processed.
  • the first and second fittings are male and female Luer lock fittings 332 and 334, respectively integral with the structure defining the restricted opening 294 and the processing vessel opening 306.
  • One of the fittings in this case the male Luer lock fitting 332, comprises a locking collar 336 with a threaded inner contact surface and defining an axially facing, generally annular first abutment 338 and the other fitting 334 comprises an axially facing, generally annular second abutment 340 facing the first abutment 338 when the fittings 332 and 334 are engaged.
  • a seal for example an O-ring 342 can be positioned between the first and second fittings 332 and 334.
  • an annular seal can be engaged between the first and second abutments 338 and 340.
  • the female Luer fitting 334 also includes dogs 344 that engage the threaded inner contact surface of the locking collar 336 to capture the O-ring 342 between the first and second fittings 332 and 334.
  • the communication established between the lumen 300 of the vessel 250 to be processed and the lumen 304 of the processing vessel 296 via the restricted opening 294 is at least substantially leak proof.
  • Luer lock fittings 332 and 334 can be made of electrically conductive material, for example stainless steel. This construction material forming or adjacent to the restricted opening 294 might contribute to formation of the plasma in the restricted opening 294.
  • the desirable volume of the lumen 304 of the processing vessel 296 is contemplated to be a trade-off between a small volume that will not divert much of the reactant flow away from the product contact surfaces desired to be coated and a large volume that will support a generous reactant gas flow rate through the restricted opening 294 before filling the lumen 304 sufficiently to reduce that flow rate to a less desirable value (by reducing the pressure difference across the restricted opening 294).
  • the contemplated volume of the lumen 304 in an embodiment, is less than three times the volume of the lumen 300 of the vessel 250 to be processed, or less than two times the volume of the lumen 300 of the vessel 250 to be processed, or less than the volume of the lumen 300 of the vessel 250 to be processed, or less than 50% of the volume of the lumen 300 of the vessel 250 to be processed, or less than 25% of the volume of the lumen 300 of the vessel 250 to be processed.
  • Other effective relationships of the volumes of the respective lumens are also contemplated.
  • the uniformity of coating can be improved in certain embodiments by repositioning the distal end of the electrode 308 relative to the vessel 250 so it does not penetrate as far into the lumen 300 of the vessel 250 as the position of the inner electrode shown in previous Figures.
  • the distal opening 316 can be positioned adjacent to the restricted opening 294, in other
  • the distal opening 316 can be positioned less than 7/8 the distance, optionally less than 3 ⁇ 4 the distance, optionally less than half the distance to the restricted opening 294 from the larger opening 302 of the vessel to be processed while feeding the reactant gas. Or, the distal opening 316 can be positioned less than 40%, less than 30%, less than 20%, less than 15%, less than 10%, less than 8%, less than 6%, less than 4%, less than 2%, or less than 1% of the distance to the restricted opening 294 from the larger opening of the vessel to be processed while feeding the reactant gas. [00162] V.B. Or, the distal end of the electrode 308 can be positioned either slightly inside or outside or flush with the larger opening 302 of the vessel 250 to be processed while
  • the positioning of the distal opening 316 relative to the vessel 250 to be processed can be optimized for particular dimensions and other conditions of treatment by testing it at various positions.
  • One particular position of the electrode 308 contemplated for treating syringe barrels 250 is with the distal end 314 penetrating about a quarter inch (about 6 mm) into the vessel lumen 300 above the larger opening 302.
  • the inventors presently contemplate that it is advantageous to place at least the distal end 314 of the electrode 308 within the vessel 250 so it will function suitably as an electrode, though that is not necessarily a requirement.
  • the plasma 318 generated in the vessel 250 can be made more uniform, extending through the restricted opening 294 into the processing vessel lumen 304, with less penetration of the electrode 308 into the lumen 300 than has previously been employed.
  • the distal end 314 of the electrode 308 commonly is placed closer to the closed end of the vessel than to its entrance.
  • the distal end 314 of the electrode 308 can be positioned at the restricted opening 294 or beyond the restricted opening 294, for example within the processing vessel lumen 304, as illustrated for example in FIG. 33.
  • Various expedients can optionally be provided, such as shaping the processing vessel 296 to improve the gas flow through the restricted opening 294.
  • the composite inner electrode and gas supply tube 398 can have distal gas supply openings such as 400, optionally located near the larger opening 302, and an extension electrode 402 extending distal of the distal gas supply openings 400, optionally extending to a distal end adjacent to the restricted opening 294, and optionally further extending into the processing vessel 324.
  • This construction is contemplated to facilitate formation of plasma within the inner contact surface 292 adjacent to the restricted opening 294.
  • the inner electrode 308, as in FIG. 26, can be moved during processing, for example, at first extending into the processing vessel lumen 304, then being withdrawn progressively proximally as the process proceeds.
  • This expedient is particularly contemplated if the vessel 250, under the selected processing conditions, is long, and movement of the inner electrode facilitates more uniform treatment of the interior contact surface 254.
  • the processing conditions such as the gas feed rate, the vacuum draw rate, the electrical energy applied to the outer electrode 160, the rate of withdrawing the inner electrode 308, or other factors can be varied as the process proceeds, customizing the process to different parts of a vessel to be treated.
  • the larger opening of the generally tubular vessel 250 to be processed can be placed on a vessel support 320, as by seating the larger opening 302 of the vessel 250 to be processed on a port 322 of the vessel support 320. Then the inner electrode 308 can be positioned within the vessel 250 seated on the vessel support 320 before drawing at least a partial vacuum within the lumen 300 of the vessel 250 to be processed.
  • the processing vessel 324 can be provided in the form of a conduit having a first opening 306 secured to the vessel 250 to be processed, as shown in FIG. 26, and a second opening 328 communicating with a vacuum port 330 in the vessel support 320.
  • the PECVD process gases can flow into the vessel 250, then via the restricted opening 294 into the processing vessel 324, then return via the vacuum port 330.
  • the vessel 250 can be evacuated through both openings 294 and 302 before applying the PECVD reactants.
  • an uncapped syringe barrel 250 can be provided with an interior coating of SiO x , in which x in this formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2, barrier or other type of PECVD coating by introducing the reactants from the source 144 through the opening at the back end 256 of the barrel 250 and drawing a vacuum using the vacuum source 98 drawing through the opening at the front end 260 of the barrel.
  • the vacuum source 98 can be connected through a second fitting 266 seated on the front end 260 of the syringe barrel 250.
  • the reactants can flow through the barrel 250 in a single direction (upward as shown in FIG. 22, though the orientation is not critical), and there is no need to convey the reactants through a probe that separates the fed gas from the exhausted gas within the syringe barrel 250.
  • the front and back ends 260 and 256 of the syringe barrel 250 can also be reversed relative to the coating apparatus, in an alternative arrangement.
  • the probe 108 can act simply as an electrode, and can either be tubular or a solid rod in this embodiment. As before, the separation between the interior contact surface 254 and the probe 108 can be uniform over at least most of the length of the syringe barrel 250.
  • FIG. 37 is a view similar to FIG. 22 showing another embodiment in which the fitting 266 is independent of and not attached to the plate electrodes 414 and 416.
  • the fitting 266 can have a Luer lock fitting adapted to be secured to the corresponding fitting of the syringe barrel 250. This embodiment allows the vacuum conduit 418 to pass over the electrode 416 while the vessel holder 420 and attached vessel 250 move between the electrodes 414 and 416 during a coating step.
  • FIG. 38 is a view similar to FIG. 22 showing still another embodiment in which the front end 260 of the syringe barrel 250 is open and the syringe barrel 250 is enclosed by a vacuum chamber 422 seated on the vessel holder 424.
  • the pressures PI within the syringe barrel 250 and within the vacuum chamber 422 are approximately identical, and the vacuum in the vacuum chamber 422 optionally is drawn through the front end 260 of the syringe barrel 250.
  • the process gases flow into the syringe barrel 250, they flow through the front end 260 of the syringe barrel 250 until a steady composition is provided within the syringe barrel 250, at which time the electrode 160 is energized to form the coating.
  • FIG. 39 is a view similar to FIG. 22 showing yet another embodiment in which the back flange of the syringe barrel 250 is clamped between a vessel holder 428 and an electrode assembly 430 to which a cylindrical electrode or pair of plate electrodes indicated as 160 and a vacuum source 98 are secured.
  • the volume generally indicated as 432 enclosed outside the syringe barrel 250 is relatively small in this embodiment to minimize the pumping needed to evacuate the volume 432 and the interior of the syringe barrel 250 to operate the PECVD process.
  • FIG. 40 is a view similar to FIG. 22 and FIG. 41 is a plan view showing even another embodiment as an alternative to FIG.
  • PI can be a lower vacuum, i.e. a higher pressure than P2 during a PECVD process so the waste process gases and by-products will pass through the front end 260 of the syringe barrel 250 and be exhausted.
  • a separate vacuum chamber conduit 436 to serve the vacuum chamber 422 allows the use of a separate vacuum pump to evacuate the greater enclosed volume 432 more quickly.
  • FIG. 41 is a plan view of the embodiment of FIG. 40, also showing the electrode 160 removed from FIG. 40.
  • V.C. Another embodiment is a method of applying a lubricity layer derived from an organosilicon precursor.
  • a "lubricity layer” or any similar term is generally defined as a coating that reduces the frictional resistance of the coated contact surface, relative to the uncoated contact surface. If the coated object is a syringe (or syringe part, e.g. syringe barrel) or any other item generally containing a plunger or movable part in sliding contact with the coated contact surface, the frictional resistance has two main aspects - breakout force and plunger sliding force.
  • the plunger sliding force test is a specialized test of the coefficient of sliding friction of the plunger within a syringe, accounting for the fact that the normal force associated with a coefficient of sliding friction as usually measured on a flat contact surface is addressed by standardizing the fit between the plunger or other sliding element and the tube or other vessel within which it slides.
  • the parallel force associated with a coefficient of sliding friction as usually measured is comparable to the plunger sliding force measured as described in this specification.
  • Plunger sliding force can be measured, for example, as provided in the ISO 7886- 1: 1993 test.
  • the plunger sliding force test can also be adapted to measure other types of frictional resistance, for example the friction retaining a stopper within a tube, by suitable variations on the apparatus and procedure.
  • the plunger can be replaced by a closure and the withdrawing force to remove or insert the closure can be measured as the counterpart of plunger sliding force.
  • the breakout force can be measured.
  • the breakout force is the force required to start a stationary plunger moving within a syringe barrel, or the comparable force required to unseat a seated, stationary closure and begin its movement.
  • the breakout force is measured by applying a force to the plunger that starts at zero or a low value and increases until the plunger begins moving.
  • the breakout force tends to increase with storage of a syringe, after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel due to decomposition of the lubricant between the plunger and the barrel.
  • the breakout force is the force needed to overcome "sticktion," an industry term for the adhesion between the plunger and barrel that needs to be overcome to break out the plunger and allow it to begin moving.
  • V.C Some utilities of coating a vessel in whole or in part with a lubricity layer, such as selectively at contact surfaces contacted in sliding relation to other parts, is to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe or a stopper in a sample tube.
  • the vessel can be made of glass or a polymer material such as polyester, for example polyethylene terephthalate (PET), a cyclic olefin copolymer (COC), an olefin such as polypropylene, or other materials.
  • Applying a lubricity layer by PECVD can avoid or reduce the need to coat the vessel wall or closure with a sprayed, dipped, or otherwise applied organosilicon or other lubricant that commonly is applied in a far larger quantity than would be deposited by a PECVD process.
  • V.C In any of the above embodiments V.C, a plasma, optionally a non-hollow- cathode plasma, optionally can be formed in the vicinity of the substrate
  • the precursor optionally can be provided in the substantial absence of oxygen.
  • V.C. In any of embodiments V.C, the precursor optionally can be provided in the substantial absence of a carrier gas.
  • V.C. In any of embodiments V.C, in which the precursor optionally can be provided in the substantial absence of nitrogen.
  • V.C. In any of embodiments V.C, in which the precursor optionally can be provided at less than 1 Torr absolute pressure.
  • the precursor optionally can be provided to the vicinity of a plasma emission.
  • the coating optionally can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10-200 nm, or 20 to 100 nm thick.
  • the thickness of this and other coatings can be measured, for example, by transmission electron microscopy (TEM).
  • the TEM can be carried out, for example, as follows.
  • Samples can be prepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Either the samples can be first coated with a thin layer of carbon (50-100nm thick) and then coated with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system, or the samples can be coated directly with the protective sputtered Pt layer.
  • the coated samples can be placed in an FEI FIB200 FIB system.
  • An additional layer of platinum can be FIB-deposited by injection of an oregano- metallic gas while rastering the 30kV gallium ion beam over the area of interest.
  • the area of interest for each sample can be chosen to be a location half way down the length of the syringe barrel.
  • Thin cross sections measuring approximately 15 ⁇ ("micrometers") long, 2 ⁇ wide and 15 ⁇ deep can be extracted from the die contact surface using a proprietary in-situ FIB lift-out technique.
  • the cross sections can be attached to a 200 mesh copper TEM grid using FIB- deposited platinum.
  • One or two windows in each section, measuring ⁇ 8 ⁇ wide, can be thinned to electron transparency using the gallium ion beam of the FEI FIB.
  • V.C. Cross-sectional image analysis of the prepared samples can be performed utilizing either a Transmission Electron Microscope (TEM), or a Scanning Transmission
  • STEM Electron Microscope
  • V.C For TEM analysis the sample grids can be transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images can be acquired at appropriate magnifications. The relevant instrument settings used during image acquisition can be those given below.
  • the substrate can comprise glass or a polymer, for example a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer or a combination of any two or more of these.
  • a polymer for example a polycarbonate polymer, an olefin polymer, a cyclic olefin copolymer, a polypropylene polymer, a polyester polymer, a polyethylene terephthalate polymer or a combination of any two or more of these.
  • the PECVD optionally can be performed by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined above, for example a frequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • a RF frequency as defined above, for example a frequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • the plasma can be generated by energizing the gaseous reactant comprising the precursor with electrodes supplied with electric power sufficient to form a lubricity layer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • These power levels are suitable for applying lubricity coatings to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • V.C One contemplated product optionally can be a syringe having a barrel treated by the method of any one or more of embodiments V.C.
  • a suitable barrier or other type of coating usable in conjunction with PECVD-applied coatings or other PECVD treatment as disclosed here, can be a liquid barrier, lubricant, contact surface energy tailoring, or other type of coating 90 applied to the interior contact surface of a vessel, either directly or with one or more intervening PECVD- applied coatings described in this specification, for example SiO x , a lubricity layer characterized as defined in the Definition Section, or both.
  • Suitable liquid barriers or other types of coatings 90 also optionally can be applied, for example, by applying a liquid monomer or other polymerizable or curable material to the interior contact surface of the vessel 80 and curing, polymerizing, or crosslinking the liquid monomer to form a solid polymer.
  • Suitable liquid barrier or other types of coatings 90 can also be provided by applying a solvent-dispersed polymer to the contact surface 88 and removing the solvent.
  • V.D Either of the above methods can include as a step forming a coating 90 on the interior 88 of a vessel 80 via the vessel port 92 at a processing station or device 28.
  • a liquid coating for example of a curable monomer, prepolymer, or polymer dispersion
  • PVdC acrylic and polyvinylidene chloride
  • V.D Either of the above methods can also or include as a step forming a coating on the exterior outer wall of a vessel 80.
  • the coating optionally can be a barrier coating, optionally an oxygen barrier coating, or optionally a water barrier coating.
  • a suitable coating is polyvinylidene chloride, which functions both as a water barrier and an oxygen barrier.
  • the barrier coating can be applied as a water-based coating.
  • the coating optionally can be applied by dipping the vessel in it, spraying it on the vessel, or other expedients.
  • a vessel having an exterior barrier coating as described above is also contemplated.
  • barrier coating 90 (shown in FIG. 2, for example), which can be an SiO x coating applied to a thickness of at least 2 nm, or at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm.
  • the coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick.
  • the thickness of the SiO x or other coating can be measured, for example, by transmission electron microscopy (TEM), and its composition can be measured by X-ray photoelectron spectroscopy (XPS).
  • TEM transmission electron microscopy
  • XPS X-ray photoelectron spectroscopy
  • Oxygen transmission is affected by the physical features of the coating, such as its thickness, the presence of cracks, and other physical details of the coating.
  • the concentration ratio of organic moieties (carbon and hydrogen compounds) to OH moieties in the deposited coating can be increased. This can be done, for example, by increasing the proportion of oxygen in the feed gases (as by increasing the oxygen feed rate or by lowering the feed rate of one or more other constituents). The lowered incidence of OH moieties is believed to result from increasing the degree of reaction of the oxygen feed with the hydrogen in the silicone source to yield more volatile water in the PECVD exhaust and a lower
  • Distortion of the medical devices can be reduced or eliminated by employing the energy in a series of two or more pulses separated by cooling time, by cooling the vessels while applying energy, by applying the coating in a shorter time (commonly thus making it thinner), by selecting a frequency of the applied coating that is absorbed minimally by the base material selected for being coated, and/or by applying more than one coating, with time in between the respective energy application steps.
  • high power pulsing can be used with a duty cycle of 1 millisecond on, 99 milliseconds off, while continuing to feed the process gas. The process gas is then the coolant, as it keeps flowing between pulses.
  • Another alternative is to reconfigure the power applicator, as by adding magnets to confine the plasma increase the effective power application (the power that actually results in incremental coating, as opposed to waste power that results in heating or unwanted coating). This expedient results in the application of more coating-formation energy per total Watt-hour of energy applied. See for example U.S. Patent 5,904,952.
  • An oxygen post-treatment of the coating can be applied to remove OH moieties from the previously-deposited coating. This treatment is also contemplated to remove residual volatile organosilicon compounds or silicones or oxidize the coating to form additional SiO x .
  • the plastic base material tube can be preheated.
  • a different volatile source of silicon such as hexamethyldisilazane (HMDZ)
  • HMDZ hexamethyldisilazane
  • changing the feed gas to HMDZ will address the problem because this compound has no oxygen moieties in it, as supplied.
  • one source of OH moieties in the HMDSO-sourced coating is hydrogenation of at least some of the oxygen atoms present in unreacted HMDSO.
  • a composite coating can be used, such as a carbon-based coating combined with SiO x . This can be done, for example, by changing the reaction conditions or by adding a substituted or unsubstituted hydrocarbon, such as an alkane, alkene, or alkyne, to the feed gas as well as an organosilicon-based compound. See for example U.S. Patent 5,904,952, which states in relevant part: "For example, inclusion of a lower hydrocarbon such as propylene provides carbon moieties and improves most properties of the deposited films (except for light transmission), and bonding analysis indicates the film to be silicon dioxide in nature. Use of methane, methanol, or acetylene, however, produces films that are silicone in nature.
  • the inclusion of a minor amount of gaseous nitrogen to the gas stream provides nitrogen moieties in the deposited films and increases the deposition rate, improves the transmission and reflection optical properties on glass, and varies the index of refraction in response to varied amounts of N 2 .
  • the addition of nitrous oxide to the gas stream increases the deposition rate and improves the optical properties, but tends to decrease the film hardness.”
  • a diamond-like carbon (DLC) coating can be formed as the primary or sole coating deposited. This can be done, for example, by changing the reaction conditions or by feeding methane, hydrogen, and helium to a PECVD process. These reaction feeds have no oxygen, so no OH moieties can be formed.
  • an SiO x coating can be applied on the interior of a tube or syringe barrel and an outer DLC coating can be applied on the exterior contact surface of a tube or syringe barrel.
  • the SiO x and DLC coatings can both be applied as a single layer or plural layers of an interior tube or syringe barrel coating.
  • the barrier or other type of coating 90 reduces the transmission of atmospheric gases into the vessel 80 through its interior contact surface 88. Or, the barrier or other type of coating 90 reduces the contact of the contents of the vessel 80 with the interior contact surface 88.
  • the barrier or other type of coating can comprise, for example, SiO x , amorphous (for example, diamond-like) carbon, or a combination of these.
  • Any coating described herein can be used for coating a contact surface, for example a plastic contact surface. It can further be used as a barrier layer, for example as a barrier against a gas or liquid, optionally against water vapor, oxygen and/or air.
  • It can also be used for preventing or reducing mechanical and/or chemical effects which the coated contact surface would have on a compound or composition if the contact surface were uncoated. For example, it can prevent or reduce the precipitation of a compound or composition, for example insulin precipitation or blood clotting or platelet activation.
  • the illustrated vessel 80 can be generally tubular, having an opening 82 at one end of the vessel, opposed by a closed end 84.
  • the vessel 80 also has a wall 86 defining an interior contact surface 88.
  • a medical sample tube such as an evacuated blood collection tube, as commonly is used by a phlebotomist for receiving a venipuncture sample of a patient's blood for use in a medical laboratory.
  • the vessel 80 can be made, for example, of thermoplastic material.
  • suitable thermoplastic material are polyethylene terephthalate or a polyolefin such as polypropylene or a cyclic polyolefin copolymer.
  • the vessel 80 can be made by any suitable method, such as by injection molding, by blow molding, by machining, by fabrication from tubing stock, or by other suitable means. PECVD can be used to form a coating on the internal contact surface of SiO x .
  • the vessel 80 desirably can be strong enough to withstand a substantially total internal vacuum substantially without deformation when exposed to an external pressure of 760 Torr or atmospheric pressure and other coating processing conditions.
  • This property can be provided, in a thermoplastic vessel 80, by providing a vessel 80 made of suitable materials having suitable dimensions and a glass transition temperature higher than the processing temperature of the coating process, for example a cylindrical wall 86 having sufficient wall thickness for its diameter and material.
  • VH.A. l. Medical vessels or containers like sample collection tubes and syringes are relatively small and are injection molded with relatively thick walls, which renders them able to be evacuated without being crushed by the ambient atmospheric pressure. They are thus stronger than carbonated soft drink bottles or other larger or thinner- walled plastic containers. Since sample collection tubes designed for use as evacuated vessels typically are constructed to withstand a full vacuum during storage, they can be used as vacuum chambers.
  • Vn.A. l Such adaptation of the vessels to be their own vacuum chambers might eliminate the need to place the vessels into a vacuum chamber for PECVD treatment, which typically is carried out at very low pressure.
  • the use of a vessel as its own vacuum chamber can result in faster processing time (since loading and unloading of the parts from a separate vacuum chamber is not necessary) and can lead to simplified equipment configurations.
  • a vessel holder is contemplated, for certain embodiments, that will hold the device (for alignment to gas tubes and other apparatus), seal the device (so that the vacuum can be created by attaching the vessel holder to a vacuum pump) and move the device between molding and subsequent processing steps.
  • a vessel 80 used as an evacuated blood collection tube should be able to withstand external atmospheric pressure, while internally evacuated to a reduced pressure useful for the intended application, without a substantial volume of air or other atmospheric gas leaking into the tube (as by bypassing the closure) or permeating through the wall 86 during its shelf life. If the as-molded vessel 80 cannot meet this requirement, it can be processed by coating the interior contact surface 88 with a barrier or other type of coating 90. It is desirable to treat and/or coat the interior contact surfaces of these devices (such as sample collection tubes and syringe barrels) to impart various properties that will offer advantages over existing polymeric devices and/or to mimic existing glass products. It is also desirable to measure various properties of the devices before and/or after treatment or coating.
  • VILA.1.a A process is contemplated for applying a lubricity layer characterized as defined in the Definition Section on a substrate, for example the interior of the barrel of a syringe, comprising applying one of the described precursors on or in the vicinity of a substrate at a thickness of 1 to 5000 nm, optionally 10 to 1000 nm, optionally 10-200 nm, optionally 20 to 100 nm thick and crosslinking or polymerizing (or both) the coating, optionally in a PECVD process, to provide a lubricated contact surface.
  • the coating applied by this process is also contemplated to be new.
  • a coating of Si w O x C y H z as defined in the Definition Section can have utility as a hydrophobic layer. Coatings of this kind are contemplated to be hydrophobic, independent of whether they function as lubricity layers. A coating or treatment is defined as "hydrophobic" if it lowers the wetting tension of a contact surface, compared to the
  • Hydrophobicity is thus a function of both the untreated substrate and the treatment.
  • the degree of hydrophobicity of a coating can be varied by varying its composition, properties, or deposition method. For example, a coating of SiOx having little or no hydrocarbon content is more hydrophilic than a coating of Si w O x C y H z as defined in the Definition Section. Generally speaking, the higher the C-H x (e.g. CH, CH 2 , or CH 3 ) moiety content of the coating, either by weight, volume, or molarity, relative to its silicon content, the more hydrophobic the coating.
  • C-H x e.g. CH, CH 2 , or CH 3
  • a hydrophobic layer can be very thin, having a thickness of at least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at least 700 nm, or at least 800 nm, or at least 900 nm.
  • the coating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm thick. Specific thickness ranges composed of any one of the minimum thicknesses expressed above, plus any equal or greater one of the maximum thicknesses expressed above, are expressly contemplated.
  • VILA.1.a One utility for such a hydrophobic layer is to isolate a thermoplastic tube wall, made for example of polyethylene terephthalate (PET), from blood collected within the tube.
  • the hydrophobic layer can be applied on top of a hydrophilic SiO x coating on the internal contact surface of the tube.
  • the SiO x coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall.
  • the hydrophobic layer can be made by providing a precursor selected from those identified in this specification.
  • the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO), octamethylcyclotetrasiloxane (OMCTS), or
  • TMDSO tetramethyldisiloxane
  • VILA.1.a Another use for a hydrophobic layer is to prepare a glass cell preparation tube.
  • the tube has a wall defining a lumen, a hydrophobic layer in the internal contact surface of the glass wall, and contains a citrate reagent.
  • the hydrophobic layer can be made by providing a precursor selected from those identified elsewhere in this specification.
  • the hydrophobic layer precursor can comprise hexamethyldisiloxane (HMDSO) or
  • OCTS octamethylcyclotetrasiloxane
  • R is a hydrogen atom or an organic substituent, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, epoxide, or others. Combinations of two or more of these are also contemplated.
  • VILA.1. Combinations of acid or base catalysis and heating, using an alkyl trimethoxysilane precursor as described above, can condense the precursor (removing ROH byproducts) to form crosslinked polymers, which can optionally be further crosslinked via an alternative method.
  • One specific example is by Shimojima et. al. J. Mater. Chem., 2007, 17, 658 - 663.
  • a lubricity layer characterized as defined in the Definition Section, can be applied as a subsequent coating after applying an SiO x barrier coating to the interior contact surface 88 of the vessel 80 to provide a lubricity layer, particularly if the lubricity layer is a liquid organosiloxane compound at the end of the coating process.
  • VILA.1.a after the lubricity layer is applied, it can be post-cured after the PECVD process. Radiation curing approaches, including UV-initiated (free radial or cationic), electron-beam (E-beam), and thermal as described in Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation, can 2008) be utilized.
  • UV-initiated free radial or cationic
  • E-beam electron-beam
  • thermal as described in Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications (Ruby Chakraborty Dissertation, can 2008) be utilized.
  • VILA.1.a. Another approach for providing a lubricity layer is to use a silicone demolding agent when injection-molding the thermoplastic vessel to be lubricated.
  • a silicone demolding agent when injection-molding the thermoplastic vessel to be lubricated.
  • any of the demolding agents and latent monomers causing in-situ thermal lubricity layer formation during the molding process can be used.
  • the aforementioned monomers can be doped into traditional demolding agents to accomplish the same result.
  • a lubricity layer characterized as defined in the Definition Section, is particularly contemplated for the internal contact surface of a syringe barrel as further described below.
  • a lubricated internal contact surface of a syringe barrel can reduce the plunger sliding force needed to advance a plunger in the barrel during operation of a syringe, or the breakout force to start a plunger moving after the prefilled syringe plunger has pushed away the intervening lubricant or adhered to the barrel, for example due to decomposition of the lubricant between the plunger and the barrel.
  • a lubricity layer also can be applied to the interior contact surface 88 of the vessel 80 to improve adhesion of a subsequent coating of SiO x .
  • the coating 90 can comprise a layer of SiO x and a lubricity layer and/or hydrophobic layer, characterized as defined in the Definition Section.
  • the lubricity layer and/or hydrophobic layer of Si w O x C y H z can be deposited between the layer of SiO x and the interior contact surface of the vessel.
  • the layer of SiO x can be deposited between the lubricity layer and/or hydrophobic layer and the interior contact surface of the vessel.
  • three or more layers, either alternating or graduated between these two coating compositions: (1) a layer of SiO x and (2) the lubricity layer and/or hydrophobic layer; can also be used.
  • the layer of SiO x can be deposited adjacent to the lubricity layer and/or hydrophobic layer or remotely, with at least one intervening layer of another material.
  • the layer of SiO x can be deposited adjacent to the interior contact surface of the vessel.
  • the lubricity layer and/or hydrophobic layer can be deposited adjacent to the interior contact surface of the vessel.
  • VILA.1.a Another expedient contemplated here, for adjacent layers of SiO x and a lubricity layer and/or hydrophobic layer, is a graded composite of Si w O x C y H z , as defined in the Definition Section.
  • a graded composite can be separate layers of a lubricity layer and/or hydrophobic layer and SiO x with a transition or interface of intermediate composition between them, or separate layers of a lubricity layer and/or hydrophobic layer and SiO x with an intermediate distinct layer of intermediate composition between them, or a single layer that changes continuously or in steps from a composition of a lubricity layer and/or hydrophobic layer to a composition more like SiO x , going through the coating in a normal direction.
  • the grade in the graded composite can go in either direction.
  • the a lubricity layer and/or hydrophobic layer can be applied directly to the substrate and graduate to a composition further from the contact surface of SiO x .
  • the composition of SiO x can be applied directly to the substrate and graduate to a composition further from the contact surface of a lubricity layer and/or hydrophobic layer.
  • a graduated coating is particularly contemplated if a coating of one composition is better for adhering to the substrate than the other, in which case the better-adhering composition can, for example, be applied directly to the substrate.
  • the more distant portions of the graded coating can be less compatible with the substrate than the adjacent portions of the graded coating, since at any point the coating is changing gradually in properties, so adjacent portions at nearly the same depth of the coating have nearly identical composition, and more widely physically separated portions at substantially different depths can have more diverse properties. It is also contemplated that a coating portion that forms a better barrier against transfer of material to or from the substrate can be directly against the substrate, to prevent the more remote coating portion that forms a poorer barrier from being contaminated with the material intended to be barred or impeded by the barrier.
  • VILA.1. The coating, instead of being graded, optionally can have sharp transitions between one layer and the next, without a substantial gradient of composition. Such coatings can be made, for example, by providing the gases to produce a layer as a steady state flow in a non- plasma state, then energizing the system with a brief plasma discharge to form a coating on the substrate. If a subsequent coating is to be applied, the gases for the previous coating are cleared out and the gases for the next coating are applied in a steady-state fashion before energizing the plasma and again forming a distinct layer on the contact surface of the substrate or its outermost previous coating, with little if any gradual transition at the interface.
  • VILA.l.b Citrate Blood Tube Having Wall Coated With Hydrophobic layer Deposited from an Organosilicon Precursor
  • VILA.1.b Another embodiment is a cell preparation tube having a wall provided with a hydrophobic layer on its inside contact surface and containing an aqueous sodium citrate reagent.
  • the hydrophobic layer can be also be applied on top of a hydrophilic SiO x coating on the internal contact surface of the tube.
  • the SiO x coating increases the barrier properties of the thermoplastic tube and the hydrophobic layer changes the contact surface energy of blood contact surface with the tube wall.
  • VILA. l.b. The wall is made of thermoplastic material having an internal contact surface defining a lumen.
  • a blood collection tube according to the embodiment VILA.1.b can have a first layer of SiO x on the internal contact surface of the tube, applied as explained in this specification, to function as an oxygen barrier and extend the shelf life of an evacuated blood collection tube made of thermoplastic material.
  • a second layer of a hydrophobic layer, characterized as defined in the Definition Section, can then be applied over the barrier layer on the internal contact surface of the tube to provide a hydrophobic contact surface.
  • the coating is effective to reduce the platelet activation of blood plasma treated with a sodium citrate additive and exposed to the inner contact surface, compared to the same type of wall uncoated.
  • VILA.1.b. PECVD is used to form a hydrophobic layer on the internal contact surface, characterized as defined in the Definition Section. Unlike conventional citrate blood collection tubes, the blood collection tube having a hydrophobic layer, characterized as defined in the Definition Section does not require a coating of baked on silicone on the vessel wall, as is conventionally applied to make the contact surface of the tube hydrophobic.
  • VILA. l.b. Both layers can be applied using the same precursor, for example HMDSO or OMCTS, and different PECVD reaction conditions.
  • VILA.1.b A sodium citrate anticoagulation reagent is then placed within the tube and it is evacuated and sealed with a closure to produce an evacuated blood collection tube.
  • the components and formulation of the reagent are known to those skilled in the art.
  • the aqueous sodium citrate reagent is disposed in the lumen of the tube in an amount effective to inhibit coagulation of blood introduced into the tube.
  • VILA.l.c SiO x Barrier Coated Double Wall Plastic Vessel- COC, PET, SiO x layers
  • VILA.1.c Another embodiment is a vessel having a wall at least partially enclosing a lumen.
  • the wall has an interior polymer layer enclosed by an exterior polymer layer.
  • One of the polymer layers is a layer at least 0.1 mm thick of a cyclic olefin copolymer (COC) resin defining a water vapor barrier.
  • Another of the polymer layers is a layer at least 0.1 mm thick of a polyester resin.
  • the wall includes an oxygen barrier layer of SiO x having a thickness of from about 10 to about 500 angstroms.
  • the vessel 80 can be a double- walled vessel having an inner wall 408 and an outer wall 410, respectively made of the same or different materials.
  • One particular embodiment of this type can be made with one wall molded from a cyclic olefin copolymer (COC) and the other wall molded from a polyester such as polyethylene terephthalate (PET), with an SiO x coating as previously described on the interior contact surface 412.
  • COC cyclic olefin copolymer
  • PET polyethylene terephthalate
  • SiO x coating as previously described on the interior contact surface 412.
  • a tie coating or layer can be inserted between the inner and outer walls to promote adhesion between them.
  • the inner wall 408 can be made of PET coated on the interior contact surface 412 with an SiO x barrier layer, and the outer wall 410 can be made of COC.
  • PET coated with SiO x is an excellent oxygen barrier, while COC is an excellent barrier for water vapor, providing a low water vapor transition rate (WVTR).
  • WVTR water vapor transition rate
  • This composite vessel can have superior barrier properties for both oxygen and water vapor.
  • This construction is contemplated, for example, for an evacuated medical sample collection tube that contains an aqueous reagent as manufactured, and has a substantial shelf life, so it should have a barrier preventing transfer of water vapor outward or transfer of oxygen or other gases inward through its composite wall during its shelf life.
  • the inner wall 408 can be made of COC coated on the interior contact surface 412 with an SiO x barrier layer, and the outer wall 410 can be made of PET.
  • This construction is contemplated, for example, for a prefilled syringe that contains an aqueous sterile fluid as manufactured.
  • the SiO x barrier will prevent oxygen from entering the syringe through its wall.
  • the COC inner wall will prevent ingress or egress of other materials such as water, thus preventing the water in the aqueous sterile fluid from leaching materials from the wall material into the syringe.
  • the COC inner wall is also contemplated to prevent water derived from the aqueous sterile fluid from passing out of the syringe (thus undesirably concentrating the aqueous sterile fluid), and will prevent non-sterile water or other fluids outside the syringe from entering through the syringe wall and causing the contents to become non- sterile.
  • the COC inner wall is also contemplated to be useful for decreasing the breaking force or friction of the plunger against the inner wall of a syringe.
  • VILA.1.d Another embodiment is a method of making a vessel having a wall having an interior polymer layer enclosed by an exterior polymer layer, one layer made of COC and the other made of polyester.
  • the vessel is made by a process including introducing COC and polyester resin layers into an injection mold through concentric injection nozzles.
  • VILA. l.d. An optional additional step is applying an amorphous carbon coating to the vessel by PECVD, as an inside coating, an outside coating, or as an interlayer coating located between the layers.
  • An optional additional step is applying an SiO x barrier layer to the inside of the vessel wall, where SiO x is defined as before.
  • Another optional additional step is post- treating the SiO x layer with a process gas consisting essentially of oxygen and essentially free of a volatile silicon compound.
  • the SiO x coating can be formed at least partially from a silazane feed gas.
  • VILA. l.d The vessel 80 shown in FIG. 36 can be made from the inside out, for one example, by injection molding the inner wall in a first mold cavity, then removing the core and molded inner wall from the first mold cavity to a second, larger mold cavity, then injection molding the outer wall against the inner wall in the second mold cavity.
  • a tie layer can be provided to the exterior contact surface of the molded inner wall before over-molding the outer wall onto the tie layer.
  • a tie layer can be provided to the interior contact surface of the molded outer wall before over-molding the inner wall onto the tie layer.
  • the vessel 80 shown in FIG. 36 can be made in a two shot mold. This can be done, for one example, by injection molding material for the inner wall from an inner nozzle and the material for the outer wall from a concentric outer nozzle.
  • a tie layer can be provided from a third, concentric nozzle disposed between the inner and outer nozzles. The nozzles can feed the respective wall materials simultaneously.
  • One useful expedient is to begin feeding the outer wall material through the outer nozzle slightly before feeding the inner wall material through the inner nozzle. If there is an intermediate concentric nozzle, the order of flow can begin with the outer nozzle and continue in sequence from the intermediate nozzle and then from the inner nozzle. Or, the order of beginning feeding can start from the inside nozzle and work outward, in reverse order compared to the preceding description.
  • VILA. l.e. Another embodiment is a vessel including a vessel, a barrier coating, and a closure.
  • the vessel is generally tubular and made of thermoplastic material.
  • the vessel has a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen.
  • a closure covers the mouth and isolates the lumen of the vessel from ambient air.
  • the vessel 80 can also be made, for example of glass of any type used in medical or laboratory applications, such as soda-lime glass, borosilicate glass, or other glass formulations.
  • Other vessels having any shape or size, made of any material, are also possible.
  • One function of coating a glass vessel can be to reduce the ingress of ions in the glass, either intentionally or as impurities, for example sodium, calcium, or others, from the glass to the contents of the vessel, such as a reagent or blood in an evacuated blood collection tube.
  • Another function of coating a glass vessel in whole or in part, such as selectively at contact surfaces contacted in sliding relation to other parts, is to provide lubricity to the coating, for example to ease the insertion or removal of a stopper or passage of a sliding element such as a piston in a syringe.
  • Still another reason to coat a glass vessel is to prevent a reagent or intended sample for the vessel, such as blood, from sticking to the wall of the vessel or an increase in the rate of coagulation of the blood in contact with the wall of the vessel.
  • VILA I.e. i.
  • a related embodiment is a vessel as described in the previous paragraph, in which the barrier coating is made of soda lime glass, borosilicate glass, or another type of glass.
  • FIGS. 23-25 illustrate a vessel 268, which can be an evacuated blood collection tube, having a closure 270 to isolate the lumen 274 from the ambient environment.
  • the closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280.
  • the closure 270 is an assembly of a stopper 282 and a shield 284.
  • VILA.2. a. Another embodiment is a method of applying a coating on an elastomeric stopper such as 282.
  • the stopper 282, separate from the vessel 268, is placed in a substantially evacuated chamber.
  • a reaction mixture is provided including plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture, which is contacted with the stopper.
  • a lubricity and/or hydrophobic layer characterized as defined in the Definition Section, is deposited on at least a portion of the stopper.
  • the wall-contacting contact surface 276 of the closure 270 is coated with a lubricity layer 286.
  • elastomeric compositions of the type useful for fabricating a stopper 282 contain trace amounts of one or more metal ions. These ions sometimes should not be able to migrate into the lumen 274 or come in substantial quantities into contact with the vessel contents, particularly if the sample vessel 268 is to be used to collect a sample for trace metal analysis. It is contemplated for example that coatings containing relatively little organic content, i.e.
  • y and z of Si w O x C y H z as defined in the Definition Section are particularly useful as a metal ion barrier in this application.
  • silica as a metal ion barrier see, for example, Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka, and Toh-Ming Lu, The Effect of Interfacial Chemistry on Metal Ion Penetration into Polymeric Films, Mat. Res. Soc. Symp. Proa, Vol. 734, pp. B9.60.1 to B9.60.6 (Materials Research Society, 2003); U.S. Patents 5578103 and 6200658, and European Appl. EP0697378 A2, which are all incorporated here by reference. It is contemplated, however, that some organic content can be useful to provide a more elastic coating and to adhere the coating to the elastomeric contact surface of the stopper 282.
  • the lubricity and/or hydrophobic layer can be a composite of material having first and second layers, in which the first or inner layer 288 interfaces with the elastomeric stopper 282 and is effective to reduce the transmission of one or more constituents of the stopper 282 into the vessel lumen.
  • the second layer 286 can interface with the inner wall 280 of the vessel and is effective as a lubricity layer to reduce friction between the stopper 282 and the inner wall 280 of the vessel when the stopper 282 is seated on or in the vessel 268.
  • Such composites are described in connection with syringe coatings elsewhere in this specification.
  • the first and second layers 288 and 286 are defined by a coating of graduated properties, in which the values of y and z defined in the Definition Section are greater in the first layer than in the second layer.
  • the lubricity and/or hydrophobic layer can be applied, for example, by PECVD substantially as previously described.
  • the lubricity and/or hydrophobic layer can be, for example, between 0.5 and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and 5000 nm thick, or between 5 and 5000 nm thick, or between 10 and 5000 nm thick, or between 20 and 5000 nm thick, or between 50 and 5000 nm thick, or between 100 and 5000 nm thick, or between 200 and 5000 nm thick, or between 500 and 5000 nm thick, or between 1000 and 5000 nm thick, or between 2000 and 5000 nm thick, or between 3000 and 5000 nm thick, or between 4000 and 10,000 nm thick.
  • Nanocoatings as applied by PECVD, are contemplated to offer lower resistance to sliding of an adjacent contact surface or flow of an adjacent fluid than micron coatings, as the plasma coating tends to provide a smoother contact surface.
  • VILA.2. a. Still another embodiment is a method of applying a coating of a lubricity and/or hydrophobic layer on an elastomeric stopper.
  • the stopper can be used, for example, to close the vessel previously described.
  • the method includes several parts.
  • a stopper is placed in a substantially evacuated chamber.
  • a reaction mixture is provided comprising plasma forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture.
  • the stopper is contacted with the reaction mixture, depositing the coating of a lubricity and/or hydrophobic layer on at least a portion of the stopper.
  • the reaction mixture can comprise a hydrocarbon gas, as further described above and below.
  • the reaction mixture can contain oxygen, if lower values of y and z or higher values of x are contemplated.
  • the reaction mixture can be essentially free of an oxidizing gas.
  • the wall-contacting and interior facing contact surfaces 276 and 272 of the stopper 282 are essentially convex, and thus readily treated by a batch process in which a multiplicity of stoppers such as 282 can be located and treated in a single substantially evacuated reaction chamber.
  • the coatings 286 and 288 do not need to present as daunting a barrier to oxygen or water as the barrier coating on the interior contact surface 280 of the vessel 268, as the material of the stopper 282 can serve this function to a large degree.
  • the stopper 282 can be contacted with the plasma.
  • the plasma can be formed upstream of the stopper 282, producing plasma product, and the plasma product can be contacted with the stopper 282.
  • the plasma can be formed by exciting the reaction mixture with electromagnetic energy and/or microwave energy.
  • the plasma forming gas can include an inert gas.
  • the inert gas can be, for example, argon or helium, or other gases described in this disclosure.
  • the organosilicon compound gas can be, or include, HMDSO, OMCTS, any of the other organosilicon compounds mentioned in this disclosure, or a combination of two or more of these.
  • the oxidizing gas can be oxygen or the other gases mentioned in this disclosure, or a combination of two or more of these.
  • the hydrocarbon gas can be, for example, methane, methanol, ethane, ethylene, ethanol, propane, propylene, propanol, acetylene, or a combination of two or more of these.
  • VII.A.2.b Another embodiment is a method of applying a coating of a composition including carbon and one or more elements of Groups III or IV on an elastomeric stopper.
  • a stopper is located in a deposition chamber.
  • VII.A.2.b A reaction mixture is provided in the deposition chamber, including a plasma forming gas with a gaseous source of a Group III element, a Group IV element, or a combination of two or more of these.
  • the reaction mixture optionally contains an oxidizing gas and optionally contains a gaseous compound having one or more C-H bonds.
  • Plasma is formed in the reaction mixture, and the stopper is contacted with the reaction mixture.
  • a coating of a Group III element or compound, a Group IV element or compound, or a combination of two or more of these is deposited on at least a portion of the stopper.
  • FIG. 1 Another embodiment is a vessel including a vessel, a barrier coating, and a closure.
  • the vessel is generally tubular and made of thermoplastic material.
  • the vessel has a mouth and a lumen bounded at least in part by a wall.
  • the wall has an inner contact surface interfacing with the lumen.
  • An at least essentially continuous barrier coating is applied on the inner contact surface of the wall.
  • the barrier coating is effective to provide a substantial shelf life.
  • a closure is provided covering the mouth of the vessel and isolating the lumen of the vessel from ambient air.
  • a vessel 268 such as an evacuated blood collection tube or other vessel is shown.
  • the vessel is, in this embodiment, a generally tubular vessel having an at least essentially continuous barrier coating and a closure.
  • the vessel is made of thermoplastic material having a mouth and a lumen bounded at least in part by a wall having an inner contact surface interfacing with the lumen.
  • the barrier coating is deposited on the inner contact surface of the wall, and is effective to maintain at least 95%, or at least 90%, of the initial vacuum level of the vessel for a shelf life of at least 24 months, optionally at least 30 months, optionally at least 36 months.
  • the closure covers the mouth of the vessel and isolates the lumen of the vessel from ambient air.
  • closure for example the closure 270 illustrated in the Figures or another type of closure, is provided to maintain a partial vacuum and/or to contain a sample and limit or prevent its exposure to oxygen or contaminants.
  • FIGS. 23-25 are based on figures found in U.S. Patent No. 6,602,206, but the present discovery is not limited to that or any other particular type of closure.
  • the closure 270 comprises a interior-facing contact surface 272 exposed to the lumen 274 of the vessel 268 and a wall-contacting contact surface 276 that is in contact with the inner contact surface 278 of the vessel wall 280.
  • the closure 270 is an assembly of a stopper 282 and a shield 284.
  • the stopper 282 defines the wall-contacting contact surface 276 and the inner contact surface 278, while the shield is largely or entirely outside the stoppered vessel 268, retains and provides a grip for the stopper 282, and shields a person removing the closure 270 from being exposed to any contents expelled from the vessel 268, such as due to a pressure difference inside and outside of the vessel 268 when the vessel 268 is opened and air rushes in or out to equalize the pressure difference.
  • the coatings on the vessel wall 280 and the wall contacting contact surface 276 of the stopper can be coordinated.
  • the stopper can be coated with a lubricity silicone layer
  • the vessel wall 280 made for example of PET or glass, can be coated with a harder SiO x layer, or with an underlying SiO x layer and a lubricity overcoat.
  • FIGS 20-22 Another example of a suitable vessel, shown in FIGS 20-22, is a syringe barrel 250 for a medical syringe 252.
  • syringes 252 are sometimes supplied prefilled with saline solution, a pharmaceutical preparation, or the like for use in medical techniques.
  • Pre-filled syringes 252 are also contemplated to benefit from an SiO x barrier or other type of coating on the interior contact surface 254 to keep the contents of the prefilled syringe 252 out of contact with the plastic of the syringe, for example of the syringe barrel 250 during storage.
  • the barrier or other type of coating can be used to avoid leaching components of the plastic into the contents of the barrel through the interior contact surface 254.
  • the front end 260 can optionally be capped and the plunger 258 optionally can be fitted in place before the prefilled syringe 252 is used, closing the barrel 250 at both ends.
  • a cap 262 can be installed either for the purpose of processing the syringe barrel 250 or assembled syringe, or to remain in place during storage of the prefilled syringe 252, up to the time the cap 262 is removed and (optionally) a hypodermic needle or other delivery conduit is fitted on the front end 260 to prepare the syringe 252 for use. VII.B.l. Assemblies
  • FIG. 42 also shows an alternative syringe barrel construction usable, for example, with the embodiments of FIGS. 21, 26, 28, 30, and 34 and adapted for use with the vessel holder 450 of that Figure..
  • FIG. 50 is an exploded view and FIG. 51 is an assembled view of a syringe.
  • the syringe barrel can be processed with the vessel treatment and inspection apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
  • VII.B.l The installation of a cap 262 makes the barrel 250 a closed-end vessel that can be provided with an SiO x barrier or other type of coating on its interior contact surface 254 in the previously illustrated apparatus, optionally also providing a coating on the interior 264 of the cap and bridging the interface between the cap interior 264 and the barrel front end 260.
  • Suitable apparatus adapted for this use is shown, for example, in FIG. 21, which is analogous to FIG. 2 except for the substitution of the capped syringe barrel 250 for the vessel 80 of FIG. 2.
  • FIG. 52 is a view similar to FIG. 42, but showing a syringe barrel being treated that has no flange or finger stops 440.
  • the syringe barrel is usable with the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-54.
  • Still another embodiment is a vessel having a lubricity layer
  • VII.B. l.a The precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • the applying step is carried out by vaporizing the precursor and providing it in the vicinity of the substrate.
  • any of the Embodiments VII.A. l.a.i optionally a plasma, optionally a non-hollow-cathode plasma, is formed in the vicinity of the substrate.
  • the precursor is provided in the substantial absence of oxygen.
  • the precursor is provided in the substantial absence of a carrier gas.
  • the precursor is provided in the substantial absence of nitrogen.
  • the precursor is provided at less than 1 Torr absolute pressure.
  • the precursor is provided to the vicinity of a plasma emission.
  • the precursor its reaction product is applied to the substrate at a thickness of 1 to 5000 nm thick, or 10 to 1000 nm thick, or 10-200 nm thick, or 20 to 100 nm thick.
  • the substrate comprises glass.
  • the substrate comprises a polymer, optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered, for example, at a RF frequency as defined above, for example a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • a RF frequency as defined above, for example a frequency of from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • VH.B.l.a Another embodiment is a lubricity layer, characterized as defined in the Definition Section, on the inner wall of a syringe barrel.
  • the coating is produced from a PECVD process using the following materials and conditions.
  • a cyclic precursor is optionally employed, selected from a monocyclic siloxane, a polycyclic siloxane, or a combination of two or more of these, as defined elsewhere in this specification for lubricity layers.
  • a suitable cyclic precursor comprises octamethylcyclotetrasiloxane (OMCTS), optionally mixed with other precursor materials in any proportion.
  • the cyclic precursor consists essentially of octamethycyclotetrasiloxane (OMCTS), meaning that other precursors can be present in amounts which do not change the basic and novel properties of the resulting lubricity layer, i.e. its reduction of the plunger sliding force or breakout force of the coated contact surface.
  • OCTS octamethycyclotetrasiloxane
  • VH.B.l.a At least essentially no oxygen, as defined in the Definition Section, is added to the process.
  • VII.B.1. Another embodiment is a vessel having a hydrophobic layer, characterized as defined in the Definition Section, on the inside wall.
  • the coating is made as explained for the lubricant coating of similar composition, but under conditions effective to form a hydrophobic contact surface having a higher contact angle than the untreated substrate.
  • the substrate comprises glass or a polymer.
  • the glass optionally is borosilicate glass.
  • the polymer is optionally a polycarbonate polymer, optionally an olefin polymer, optionally a cyclic olefin copolymer, optionally a polypropylene polymer, optionally a polyester polymer, optionally a polyethylene terephthalate polymer.
  • a syringe including a plunger, a syringe barrel, and a lubricity layer, characterized as defined in the Definition Section.
  • the syringe barrel includes an interior contact surface receiving the plunger for sliding.
  • the lubricity layer is disposed on the interior contact surface of the syringe barrel.
  • the lubricity layer is less than 1000 nm thick and effective to reduce the breakout force or the plunger sliding force necessary to move the plunger within the barrel. Reducing the plunger sliding force is alternatively expressed as reducing the coefficient of sliding friction of the plunger within the barrel or reducing the plunger force; these terms are regarded as having the same meaning in this specification.
  • the syringe 544 of FIGS. 50-51 comprises a plunger 546 and a syringe barrel 548.
  • the syringe barrel 548 has an interior contact surface 552 receiving the plunger for sliding 546.
  • the interior contact surface 552 of the syringe barrel 548 further comprises a lubricity layer 554, characterized as defined in the Definition Section.
  • the lubricity layer is less than 1000 nm thick, optionally less than 500 nm thick, optionally less than 200 nm thick, optionally less than 100 nm thick, optionally less than 50 nm thick, and is effective to reduce the breakout force necessary to overcome adhesion of the plunger after storage or the plunger sliding force necessary to move the plunger within the barrel after it has broken away.
  • the lubricity layer is characterized by having a plunger sliding force or breakout force lower than that of the uncoated contact surface.
  • VH.B.l.a Any of the above precursors of any type can be used alone or in combinations of two or more of them to provide a lubricity layer.
  • VH.B.l.a In addition to utilizing vacuum processes, low temperature atmospheric (non-vacuum) plasma processes can also be utilized to induce molecular ionization and deposition through precursor monomer vapor delivery optionally in a non-oxidizing atmosphere such as helium or argon. Separately, thermal CVD can be considered via flash thermolysis deposition.
  • VH.B.l.a The approaches above are similar to vacuum PECVD in that the contact surface coating and crosslinking mechanisms can occur simultaneously.
  • VH.B.l.a Yet another expedient contemplated for any coating or coatings described here is a coating that is not uniformly applied over the entire interior 88 of a vessel. For example, a different or additional coating can be applied selectively to the cylindrical portion of the vessel interior, compared to the hemispherical portion of the vessel interior at its closed end 84, or vice versa. This expedient is particularly contemplated for a syringe barrel or a sample collection tube as described below, in which a lubricity layer might be provided on part or all of the cylindrical portion of the barrel, where the plunger or piston or closure slides, and not elsewhere. [00301] VH.B.l.a.
  • the precursor can be provided in the presence, substantial absence, or absence of oxygen, in the presence, substantial absence, or absence of nitrogen, or in the presence, substantial absence, or absence of a carrier gas.
  • the precursor alone is delivered to the substrate and subjected to PECVD to apply and cure the coating.
  • the precursor can be provided at less than 1 Torr absolute pressure.
  • the precursor can be provided to the vicinity of a plasma emission.
  • the precursor its reaction product can be applied to the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm., or 10-200 nm, or 20 to 100 nm.
  • the substrate can comprise glass, or a polymer, for example one or more of a polycarbonate polymer, an olefin polymer (for example a cyclic olefin copolymer or a polypropylene polymer), or a polyester polymer (for example, a polyethylene terephthalate polymer).
  • a polymer for example one or more of a polycarbonate polymer, an olefin polymer (for example a cyclic olefin copolymer or a polypropylene polymer), or a polyester polymer (for example, a polyethylene terephthalate polymer).
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes powered at a RF frequency as defined in this description.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with sufficient electric power to generate a lubricity layer.
  • the plasma is generated by energizing the gaseous reactant containing the precursor with electrodes supplied with an electric power of from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally 8 W.
  • the ratio of the electrode power to the plasma volume can be less than 10 W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to 0.2 W/ml.
  • These power levels are suitable for applying lubricity layers to syringes and sample tubes and vessels of similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is generated. It is contemplated that for larger or smaller objects the power applied should be increased or reduced accordingly to scale the process to the size of the substrate.
  • the coating can be cured, as by polymerizing or crosslinking the coating, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate. Curing can occur during the application process such as PECVD, or can be carried out or at least completed by separate processing.
  • VH.B.l.a Although plasma deposition has been used herein to demonstrate the coating characteristics, alternate deposition methods can be used as long as the chemical composition of the starting material is preserved as much as possible while still depositing a solid film that is adhered to the base substrate.
  • the coating material can be applied onto the syringe barrel (from the liquid state) by spraying the coating or dipping the substrate into the coating, where the coating is either the neat precursor a solvent-diluted precursor (allowing the mechanical deposition of a thinner coating).
  • the coating optionally can be crosslinked using thermal energy, UV energy, electron beam energy, plasma energy, or any combination of these.
  • VH.B.l.a Application of a silicone precursor as described above onto a contact surface followed by a separate curing step is also contemplated.
  • the conditions of application and curing can be analogous to those used for the atmospheric plasma curing of pre-coated polyfluoroalkyl ethers, a process practiced under the trademark TriboGlide®. More details of this process can be found at http://www.triboglide.com/process.htm.
  • the area of the part to be coated can optionally be pre- treated with an atmospheric plasma. This pretreatment cleans and activates the contact surface so that it is receptive to the lubricant that is sprayed in the next step.
  • VII.B.l.a The lubrication fluid, in this case one of the above precursors or a polymerized precursor, is then sprayed on to the contact surface to be treated.
  • IVEK precision dispensing technology can be used to accurately atomize the fluid and create a uniform coating.
  • VH.B.l.a The coating is then bonded or crosslinked to the part, again using an atmospheric plasma field. This both immobilizes the coating and improves the lubricant's performance.
  • the atmospheric plasma can be generated from ambient air in the vessel, in which case no gas feed and no vacuum drawing equipment is needed.
  • the vessel is at least substantially closed while plasma is generated, to minimize the power requirement and prevent contact of the plasma with contact surfaces or materials outside the vessel.
  • Lubricity layer SiO x Barrier, Lubricity Layer, Contact surface Treatment Contact surface treatment
  • VH.B.l.a.i. Another embodiment is a syringe comprising a barrel defining a lumen and having an interior contact surface slidably receiving a plunger, i.e. receiving a plunger for sliding contact to the interior contact surface.
  • VH.B.l.a.i The syringe barrel is made of thermoplastic base material.
  • VH.B.l.a.i the interior contact surface of the barrel is coated with an SiO x barrier layer as described elsewhere in this specification.
  • VH.B.l.a.i A lubricity layer is applied to the barrel interior contact surface, the plunger, or both, or to the previously applied SiO x barrier layer.
  • the lubricity layer can be provided, applied, and cured as set out in embodiment VH.B.l.a or elsewhere in this
  • the lubricity layer can be applied, in any embodiment, by PECVD.
  • the lubricity layer is deposited from an organosilicon precursor, and is less than 1000 nm thick.
  • a contact surface treatment is carried out on the lubricity layer in an amount effective to reduce the leaching or extractables of the lubricity layer, the thermoplastic base material, or both.
  • the treated contact surface can thus act as a solute retainer.
  • This contact surface treatment can result in a skin coating, e.g.
  • a skin coating which is at least 1 nm thick and less than 100 nm thick, or less than 50 nm thick, or less than 40 nm thick, or less than 30 nm thick, or less than 20 nm thick, or less than 10 nm thick, or less than 5 nm thick, or less than 3 nm thick, or less than 2 nm thick, or less than 1 nm thick, or less than 0.5 nm thick.
  • leaching refers to material transferred out of a substrate, such as a vessel wall, into the contents of a vessel, for example a syringe. Commonly, leachables are measured by storing the vessel filled with intended contents, then analyzing the contents to determine what material leached from the vessel wall into the intended contents. “Extraction” refers to material removed from a substrate by introducing a solvent or dispersion medium other than the intended contents of the vessel, to determine what material can be removed from the substrate into the extraction medium under the conditions of the test.
  • the contact surface treatment resulting in a solute retainer optionally can be a SiO x layer as previously defined in this specification or a hydrophobic layer, characterized as defined in the Definition Section.
  • the contact surface treatment can be applied by PECVD deposit of SiO x or a hydrophobic layer.
  • the contact surface treatment can be applied using higher power or stronger oxidation conditions than used for creating the lubricity layer, or both, thus providing a harder, thinner, continuous solute retainer 539.
  • Contact surface treatment can be less than 100 nm deep, optionally less than 50 nm deep, optionally less than 40 nm deep, optionally less than 30 nm deep, optionally less than 20 nm deep, optionally less than 10 nm deep, optionally less than 5 nm deep, optionally less than 3 nm deep, optionally less than 1 nm deep, optionally less than 0.5 nm deep, optionally between 0.1 and 50 nm deep in the lubricity layer.
  • the solute retainer is contemplated to provide low solute leaching performance to the underlying lubricity and other layers, including the substrate, as required.
  • This retainer would only need to be a solute retainer to large solute molecules and oligomers (for example siloxane monomers such as HMDSO, OMCTS, their fragments and mobile oligomers derived from lubricants, for example a "leachables retainer") and not a gas (Oi/Ni/CC water vapor) barrier layer.
  • a solute retainer can, however, also be a gas barrier (e.g. the SiOx coating according to present invention.
  • the "leachables barrier” will be sufficiently thin that, upon syringe plunger movement, the plunger will readily penetrate the "solute retainer” exposing the sliding plunger nipple to the lubricity layer immediately below to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • the contact surface treatment can be performed by oxidizing the contact surface of a previously applied lubricity layer, as by exposing the contact surface to oxygen in a plasma environment.
  • the plasma environment described in this specification for forming SiO x coatings can be used.
  • atmospheric plasma conditions can be employed in an oxygen-rich environment.
  • the lubricity layer and solute retainer optionally can be cured at the same time.
  • the lubricity layer can be at least partially cured, optionally fully cured, after which the contact surface treatment can be provided, applied, and the solute retainer can be cured.
  • the lubricity layer and solute retainer are composed, and present in relative amounts, effective to provide a breakout force, plunger sliding force, or both that is less than the corresponding force required in the absence of the lubricity layer and contact surface treatment.
  • the thickness and composition of the solute retainer are such as to reduce the leaching of material from the lubricity layer into the contents of the syringe, while allowing the underlying lubricity layer to lubricate the plunger. It is contemplated that the solute retainer will break away easily and be thin enough that the lubricity layer will still function to lubricate the plunger when it is moved.
  • the lubricity and contact surface treatments can be applied on the barrel interior contact surface. In another contemplated embodiment, the lubricity and contact surface treatments can be applied on the plunger. In still another contemplated embodiment, the lubricity and contact surface treatments can be applied both on the barrel interior contact surface and on the plunger. In any of these embodiments, the optional SiO x barrier layer on the interior of the syringe barrel can either be present or absent.
  • VH.B.l.a.i One embodiment contemplated is a plural-layer, e.g. a 3-layer, configuration applied to the inside contact surface of a syringe barrel.
  • Layer 1 can be an SiO x gas barrier made by PECVD of HMDSO, OMCTS, or both, in an oxidizing atmosphere. Such an atmosphere can be provided, for example, by feeding HMDSO and oxygen gas to a PECVD coating apparatus as described in this specification.
  • Layer 2 can be a lubricity layer using OMCTS applied in a non-oxidizing atmosphere. Such a non-oxidizing atmosphere can be provided, for example, by feeding OMCTS to a PECVD coating apparatus as described in this specification, optionally in the substantial or complete absence of oxygen.
  • a subsequent solute retainer can be formed by a treatment forming a thin skin layer of SiO x or a hydrophobic layer as a solute retainer using higher power and oxygen using OMCTS and/or HMDSO.
  • VH.B.l.a.i Certain of these plural-layer coatings are contemplated to have one or more of the following optional advantages, at least to some degree. They can address the reported difficulty of handling silicone, since the solute retainer can confine the interior silicone and prevent if from migrating into the contents of the syringe or elsewhere, resulting in fewer silicone particles in the deliverable contents of the syringe and less opportunity for interaction between the lubricity layer and the contents of the syringe. They can also address the issue of migration of the lubricity layer away from the point of lubrication, improving the lubricity of the interface between the syringe barrel and the plunger. For example, the break-free force can be reduced and the drag on the moving plunger can be reduced, or optionally both.
  • VH.B.l.a.i It is contemplated that when the solute retainer is broken, the solute retainer will continue to adhere to the lubricity layer and the syringe barrel, which can inhibit any particles from being entrained in the deliverable contents of the syringe.
  • VH.B.l.a.i Certain of these coatings will also provide manufacturing advantages, particularly if the barrier coating, lubricity layer and contact surface treatment are applied in the same apparatus, for example the illustrated PECVD apparatus.
  • the SiO x barrier coating, lubricity layer, and contact surface treatment can all be applied in one PECVD apparatus, thus greatly reducing the amount of handling necessary.
  • barrier coating can be formed using the same precursors and varying the process.
  • an SiO x gas barrier layer can be applied using an OMCTS precursor under high power/high 0 2 conditions, followed by applying a lubricity layer applied using an OMCTS precursor under low power and/or in the substantial or complete absence of oxygen, finishing with a contact surface treatment using an OMCTS precursor under intermediate power and oxygen.
  • VII.B.l.b Syringe having barrel with SiO x coated interior and barrier coated exterior
  • a syringe 544 including a plunger 546, a barrel 548, and interior and exterior barrier coatings 554 and 602.
  • the barrel 548 can be made of thermoplastic base material defining a lumen 604.
  • the barrel 548 can have an interior contact surface 552 receiving the plunger for sliding 546 and an exterior contact surface 606.
  • a barrier coating 554 of SiO x in which x is from about 1.5 to about 2.9, can be provided on the interior contact surface 552 of the barrel 548.
  • a barrier coating 602 of a resin can be provided on the exterior contact surface 606 of the barrel 548.
  • the thermoplastic base material optionally can include a polyolefin, for example polypropylene or a cyclic olefin copolymer (for example the material sold under the trademark TOPAS®), a polyester, for example polyethylene terephthalate, a polycarbonate, for example a bisphenol A polycarbonate thermoplastic, or other materials.
  • a polyolefin for example polypropylene or a cyclic olefin copolymer (for example the material sold under the trademark TOPAS®)
  • a polyester for example polyethylene terephthalate
  • a polycarbonate for example a bisphenol A polycarbonate thermoplastic, or other materials.
  • Composite syringe barrels are contemplated having any one of these materials as an outer layer and the same or a different one of these materials as an inner layer. Any of the material combinations of the composite syringe barrels or sample tubes described elsewhere in this specification can also be used.
  • the resin optionally can include polyvinylidene chloride in homopolymer or copolymer form.
  • the PVdC homopolymers (trivial name: Saran) or copolymers described in US Patent 6,165,566, incorporated here by reference, can be employed.
  • the resin optionally can be applied onto the exterior contact surface of the barrel in the form of a latex or other dispersion.
  • the syringe barrel 548 optionally can include a lubricity layer disposed between the plunger and the barrier coating of SiO x . Suitable lubricity layers are described elsewhere in this specification.
  • the lubricity layer optionally can be applied by PECVD and optionally can include material characterized as defined in the Definition Section.
  • the syringe barrel 548 optionally can include a contact surface treatment covering the lubricity layer in an amount effective to reduce the leaching of the lubricity layer, constituents of the thermoplastic base material, or both into the lumen 604.
  • VII.B.l.c Even another embodiment is a method of making a syringe as described in any of the embodiments of part VII.B. l.b, including a plunger, a barrel, and interior and exterior barrier coatings.
  • a barrel is provided having an interior contact surface for receiving the plunger for sliding and an exterior contact surface.
  • a barrier coating of SiO x is provided on the interior contact surface of the barrel by PECVD.
  • a barrier coating of a resin is provided on the exterior contact surface of the barrel.
  • the plunger and barrel are assembled to provide a syringe.
  • the resin optionally can be applied via dip coating of the latex onto the exterior contact surface of the barrel, spray coating of the latex onto the exterior contact surface of the barrel, or both, providing plastic-based articles offering improved gas and vapor barrier performance.
  • Polyvinylidene chloride plastic laminate articles can be made that provide significantly improved gas barrier performance versus the non-laminated plastic article.
  • the resin optionally can be heat cured.
  • the resin optionally can be cured by removing water. Water can be removed by heat curing the resin, exposing the resin to a partial vacuum or low-humidity environment, catalytically curing the resin, or other expedients.
  • VII.B.l.c An effective thermal cure schedule is contemplated to provide final drying to permit PVdC crystallization, offering barrier performance.
  • Primary curing can be carried out at an elevated temperature, for example between 180-310°F (82-154°C), of course depending on the heat tolerance of the thermoplastic base material.
  • Barrier performance after the primary cure optionally can be about 85% of the ultimate barrier performance achieved after a final cure.
  • a final cure can be carried out at temperatures ranging from ambient temperature, such as about 65-75°F (18-24°C) for a long time (such as 2 weeks) to an elevated temperature, such as 122°F (50°C), for a short time, such as four hours.
  • PVdC -plastic laminate articles in addition to superior barrier performance, are optionally contemplated to provide one or more desirable properties such as colorless transparency, good gloss, abrasion resistance, printability, and mechanical strain resistance.
  • a plunger for a syringe including a piston and a push rod.
  • the piston has a front face, a generally cylindrical side face, and a back portion, the side face being configured to movably seat within a syringe barrel.
  • the front face has a barrier coating.
  • the push rod engages the back portion and is configured for advancing the piston in a syringe barrel.
  • a plunger for a syringe including a piston, a lubricity layer, and a push rod.
  • the piston has a front face, a generally cylindrical side face, and a back portion.
  • the side face is configured to movably seat within a syringe barrel.
  • the lubricity layer interfaces with the side face.
  • the push rod engages the back portion of the piston and is configured for advancing the piston in a syringe barrel.
  • a syringe including a plunger, a syringe barrel, and a Luer fitting.
  • the syringe includes a barrel having an interior contact surface receiving the plunger for sliding.
  • the Luer fitting includes a Luer taper having an internal passage defined by an internal contact surface.
  • the Luer fitting is formed as a separate piece from the syringe barrel and joined to the syringe barrel by a coupling.
  • the internal passage of the Luer taper has a barrier coating of SiO x .
  • the syringe 544 optionally can include a Luer fitting 556 comprising a Luer taper 558 to receive a cannula mounted on a complementary Luer taper (not shown, conventional).
  • the Luer taper 558 has an internal passage 560 defined by an internal contact surface 562.
  • the Luer fitting 556 optionally is formed as a separate piece from the syringe barrel 548 and joined to the syringe barrel 548 by a coupling 564.
  • the coupling 564 in this instance has a male part 566 and a female part 568 that snap together to secure the Luer fitting in at least substantially leak proof fashion to the barrel 548.
  • the internal contact surface 562 of the Luer taper can include a barrier coating 570 of SiO x .
  • the barrier coating can be less than 100 nm thick and effective to reduce the ingress of oxygen into the internal passage of the Luer fitting.
  • the barrier coating can be applied before the Luer fitting is joined to the syringe barrel.
  • the syringe of FIGS. 50-51 also has an optional locking collar 572 that is internally threaded so to lock the complementary Luer taper of a cannula in place on the taper 558.
  • Still another embodiment is a lubricity layer.
  • This coating can be of the type made by the following process.
  • any of the precursors mentioned elsewhere in this specification can be used, alone or in combination.
  • the precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • VII.B.4. a. Another embodiment is a method of applying a lubricity layer.
  • An organosilicon precursor is applied to a substrate under conditions effective to form a coating.
  • the coating is polymerized or crosslinked, or both, to form a lubricated contact surface having a lower plunger sliding force or breakout force than the untreated substrate.
  • Even another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has a density between 1.25 and 1.65 g/cm optionally between 1.35 and 1.55 g/cm 3 , optionally between 1.4 and 1.5 g/cm 3 , optionally between 1.44 and 1.48 g/cm 3 as determined by X-ray reflectivity (XRR).
  • XRR X-ray reflectivity
  • Still another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising an organometallic precursor, optionally an organosilicon precursor, optionally a linear siloxane, a linear silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has as an outgas component one or more oligomers containing repeating - (Me) 2 SiO- moieties, as determined by gas chromatography / mass spectrometry.
  • the coating meets the limitations of any of embodiments VII.B.4.a or VII.B.4.b.A.585h.
  • the coating outgas component as determined by gas chromatography / mass spectrometry is substantially free of trimethylsilanol.
  • the coating outgas component can be at least 10 ng/test of oligomers containing repeating -(Me) 2 SiO- moieties, as determined by gas chromatography / mass spectrometry using the following test conditions:
  • MSD Mass Selective Detector
  • the outgas component can include at least 20 ng/test of oligomers containing repeating -(Me) 2 SiO- moieties.
  • the feed gas comprises a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these, for example a monocyclic siloxane, a monocyclic silazane, or any combination of two or more of these, for example octamethylcyclotetrasiloxane.
  • the lubricity layer of any embodiment can have a thickness measured by transmission electron microscopy (TEM) between 1 and 500 nm, optionally between 10 and 500 nm, optionally between 20 and 200 nm, optionally between 20 and 100 nm, optionally between 30 and 100 nm.
  • TEM transmission electron microscopy
  • VII.BAb Another aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has an atomic concentration of carbon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), greater than the atomic concentration of carbon in the atomic formula for the feed gas.
  • XPS X-ray photoelectron spectroscopy
  • the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
  • the atomic concentration of carbon increases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic percent, alternatively from 37 to 41 atomic percent.
  • VTI.BAb An additional aspect of the invention is a lubricity layer deposited by PECVD from a feed gas comprising a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of two or more of these.
  • the coating has an atomic concentration of silicon, normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS), less than the atomic concentration of silicon in the atomic formula for the feed gas.
  • XPS X-ray photoelectron spectroscopy
  • the coating meets the limitations of embodiments VII.BAa or VII.BAb.A.
  • VII.BAb Optionally, the atomic concentration of silicon decreases by from 1 to 80 atomic percent (as calculated and based on the XPS conditions in Example 15), alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic percent, alternatively from 30 to 55 atomic percent, alternatively from 40 to 50 atomic percent, alternatively from 42 to 46 atomic percent.
  • VII.BAb Lubricity layers having combinations of any two or more properties recited in Section VII.B.4 are also expressly contemplated.
  • a coated vessel or container as described herein and/or prepared according to a method described herein can be used for reception and/or storage and/or delivery of a compound or composition.
  • the compound or composition can be sensitive, for example air- sensitive, oxygen-sensitive, sensitive to humidity and/or sensitive to mechanical influences. It can be a biologically active compound or composition, for example a medicament like insulin or a composition comprising insulin. In another aspect, it can be a biological fluid, optionally a bodily fluid, for example blood or a blood fraction.
  • the compound or composition is a product to be administrated to a subject in need thereof, for example a product to be injected, like blood (as in transfusion of blood from a donor to a recipient or reintroduction of blood from a patient back to the patient) or insulin.
  • a product to be injected like blood (as in transfusion of blood from a donor to a recipient or reintroduction of blood from a patient back to the patient) or insulin.
  • a coated vessel or container as described herein and/or prepared according to a method described herein can further be used for protecting a compound or composition contained in its interior space against mechanical and/or chemical effects of the contact surface of the uncoated vessel material. For example, it can be used for preventing or reducing precipitation and/or clotting or platelet activation of the compound or a component of the composition, for example insulin precipitation or blood clotting or platelet activation.
  • VII.C It can further be used for protecting a compound or composition contained in its interior against the environment outside of the vessel, for example by preventing or reducing the entry of one or more compounds from the environment surrounding the vessel into the interior space of the vessel.
  • Such environmental compound can be a gas or liquid, for example an atmospheric gas or liquid containing oxygen, air, and/or water vapor.
  • a coated vessel as described herein can also be evacuated and stored in an evacuated state.
  • the coating allows better maintenance of the vacuum in comparison to a corresponding uncoated vessel.
  • the coated vessel is a blood collection tube.
  • the tube can also contain an agent for preventing blood clotting or platelet activation, for example EDTA or heparin.
  • any of the above-described embodiments can be made, for example, by providing as the vessel a length of tubing from about 1 cm to about 200 cm, optionally from about 1 cm to about 150 cm, optionally from about 1 cm to about 120 cm, optionally from about 1 cm to about 100 cm, optionally from about 1 cm to about 80 cm, optionally from about 1 cm to about 60 cm, optionally from about 1 cm to about 40 cm, optionally from about 1 cm to about 30 cm long, and processing it with a probe electrode as described below.
  • relative motion between the probe and the vessel can be useful during coating formation. This can be done, for example, by moving the vessel with respect to the probe or moving the probe with respect to the vessel.
  • the coating can be thinner or less complete than can be preferred for a barrier coating, as the vessel in some embodiments will not require the high barrier integrity of an evacuated blood collection tube.
  • the vessel has a central axis.
  • the vessel wall is sufficiently flexible to be flexed at least once at 20 °C, without breaking the wall, over a range from at least substantially straight to a bending radius at the central axis of not more than 100 times as great as the outer diameter of the vessel.
  • the bending radius at the central axis is not more than 90 times as great as, or not more than 80 times as great as, or not more than 70 times as great as, or not more than 60 times as great as, or not more than 50 times as great as, or not more than 40 times as great as, or not more than 30 times as great as, or not more than 20 times as great as, or not more than 10 times as great as, or not more than 9 times as great as, or not more than 8 times as great as, or not more than 7 times as great as, or not more than 6 times as great as, or not more than 5 times as great as, or not more than 4 times as great as, or not more than 3 times as great as, or not more than 2 times as great as, or not more than, the outer diameter of the vessel.
  • the vessel wall can be a fluid-contacting contact surface made of flexible material.
  • the vessel lumen can be the fluid flow passage of a pump.
  • the vessel can be a blood bag adapted to maintain blood in good condition for medical use.
  • the polymeric material can be a silicone elastomer or a thermoplastic polyurethane, as two examples, or any material suitable for contact with blood, or with insulin.
  • the vessel has an inner diameter of at least 2 mm, or at least 4 mm.
  • the vessel is a tube.
  • the lumen has at least two open ends.
  • Even another embodiment is a blood containing vessel.
  • a blood transfusion bag a blood sample collection vessel in which a sample has been collected
  • the tubing of a heart-lung machine a flexible-walled blood collection bag, or tubing used to collect a patient' s blood during surgery and reintroduce the blood into the patient's vasculature.
  • a particularly suitable pump is a centrifugal pump or a peristaltic pump.
  • the vessel has a wall; the wall has an inner contact surface defining a lumen.
  • the inner contact surface of the wall has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section.
  • the coating can be as thin as monomolecular thickness or as thick as about 1000 nm.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • An embodiment is a blood containing vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer.
  • the coating can also comprise or consist essentially of SiO x , where x is as defined in this specification.
  • the thickness of the coating is within the range from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • VII.C.2. Another embodiment is a vessel having a wall.
  • the wall has an inner contact surface defining a lumen and has an at least partial coating of a hydrophobic layer, where optionally w, x, y, and z are as previously defined in the Definition Section.
  • the thickness of the coating is from monomolecular thickness to about 1000 nm thick on the inner contact surface. The coating is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface, compared to the same type of wall uncoated with a hydrophobic layer.
  • VII.C.2. Another embodiment is a vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface, the coating being effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface.
  • Another embodiment is a blood containing vessel having a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a composition comprising one or more elements of Group III, one or more elements of Group IV , or a combination of two or more of these.
  • the thickness of the coating is between monomolecular thickness and about 1000 nm thick, inclusive, on the inner contact surface.
  • the vessel contains blood viable for return to the vascular system of a patient disposed within the lumen in contact with the hydrophobic layer.
  • the coating of the Group III or IV Element is effective to reduce the clotting or platelet activation of blood exposed to the inner contact surface of the vessel wall.
  • a coated vessel or container as described herein can be used for preventing or reducing the escape of a compound or composition contained in the vessel into the environment surrounding the vessel.
  • Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section.
  • the coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • Insulin is disposed within the lumen in contact with the Si w O x C y H z coating.
  • Still another embodiment is an insulin containing vessel including a wall and having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a hydrophobic layer, characterized as defined in the Definition Section, the thickness of the coating being from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • Insulin for example pharmaceutical insulin FDA approved for human use, is disposed within the lumen in contact with the hydrophobic layer.
  • hydrophobic layer characterized as defined in the Definition Section, will reduce the adhesion or precipitation forming tendency of the insulin in a delivery tube of an insulin pump, as compared to its properties in contact with an unmodified polymeric contact surface. This property is
  • the coating of a hydrophobic layer is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the hydrophobic layer.
  • Even another embodiment is a vessel again comprising a wall and having an inner contact surface defining a lumen.
  • the inner contact surface includes an at least partial coating of a hydrophobic layer.
  • the thickness of the coating is in the range from monomolecular thickness to about 1000 nm thick on the inner contact surface.
  • the coating is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface.
  • FIG. 1 Another embodiment is an insulin containing vessel including a wall having an inner contact surface defining a lumen.
  • the inner contact surface has an at least partial coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these.
  • the coating can be from monomolecular thickness to about 1000 nm thick on the inner contact surface. Insulin is disposed within the lumen in contact with the coating.
  • the coating of a composition comprising carbon, one or more elements of Group III, one or more elements of Group IV, or a combination of two or more of these is effective to reduce the formation of a precipitate from insulin contacting the inner contact surface, compared to the same contact surface absent the coating.
  • a second antimicrobially effective treatment is applied to the contact surface with its first treatment.
  • the second treatment is a treatment of a metal selected from silver, gold, platinum, copper, tantalum, titanium, zirconium, hafnium, or zinc, or a compound of the metal, applied to the contact surface with its first treatment.
  • antimicrobial agent is silver or a silver compound.
  • Suitable antimicrobial treatments include the following.
  • a silver ion coating is applied by dip or paint to inhibit infections in invasive medical devices and to create burn and wound treatments.
  • the device must be properly prepared first through sterilization and removal of debris before any coating process is performed.
  • This traditional coating method has worked well, and several companies have proprietary application methods using nano-sized silver crystals for wound treatments.
  • Devices and wound dressings treated with silver must be able to withstand the high heat associated with coating technologies. For example, certain coating technologies, such as plating, could not be used to apply silver oxide to a gauze bandage or disposable diaper-the fabric would disintegrate.
  • silver is used in conjunction with certain surfaces or coatings.
  • many medical devices such as catheters, are manufactured with a hydrophobic polymer matrix, which limits the silver ion concentration near the device surface.
  • Silver oxide requires the presence of moisture to release its anti-microbial properties. Affixing silver oxide to a hydrophobic polymer reduces the moisture present and thus decreases silver's antimicrobial effect.
  • Commercially available devices coated with these processes may experience limited effectiveness.
  • silver-antimicrobial compounds address this problem by adding silver mixed with a ceramic, such as zirconium phosphate, directly into the polymer material before it is manufactured into a medical device.
  • a ceramic such as zirconium phosphate
  • incorporation of the antimicrobial material into the polymer from which the contact surface is made is regarded as an antimicrobial treatment of the surface.
  • iontophoric polymers are designed to release silver ions when wet with body fluids.
  • an electrolytic fluid such as saline, blood, drug preparations, or urine
  • the metal powders become a mass of tiny electrodes.
  • Each molecule becomes an anode or a cathode, making the polymer conductive, which causes it to release the silver ions.
  • the ion exchange is a slow process, which is a benefit because it may extend the antimicrobial effect.8
  • This application technique has been used in catheters. Other uses being explored include orthopedic implants, pacemaker leads, suture leads, and feeding tubes.
  • the newest innovation for silver oxide antimicrobials involves surface-engineered ordered nanostructures of silver oxide that are built on the medical device surface.
  • the approach employs nanotechnology to apply antimicrobial silver to medical devices.
  • Nanotechnology may provide the most effective platform to maximize the antimicrobial capability of silver.
  • the nanostructures comprise silver particles. Because each tiny particle in a nanostmcture has its own surface area, it increases the overall surface area of the silver oxide. A larger surface area means more silver can interact with body fluids to encounter and inhibit microbes. Surface engineering of ordered nanostructures takes place on the nanometer scale.
  • IPD ionic plasma deposition
  • Depositing material ions are accelerated to ensure that the depositing species are the correct energy for the desired process and for the medical device polymer material. This allows for a broad range of custom stoichiometries and demonstrates that IPD technology is adaptable when used to treat medical polymers.
  • Low-temperature polymers are used in soft-tissue implants. These polymers, such as polyethylene, polyester, polypropylene, and even Teflon (PTFE), can be treated with IPD nanotechnology.
  • IPD can be controlled for particle size, density, and rate of deposition. Because it incorporates a high degree of control and low heat application, IPD also has traits of adhesion and repeatability for silver application. The structures are laid down in a highly ordered surface. Deposition is possible in concentric plasma to almost any length. Source-material use is very efficient, so that high- volume precious-metal applications such as silver, platinum, and gold are economical.
  • Silver oxide application should maintain conformal quality of the medical device surface regardless of surface morphology.
  • the silver is deposited into blind holes, vias, and cavities with aspect ratios of 5: 1. Coatings are now measured in angstroms, and application layers must be extremely thin.9 IPD surface-engineered
  • nanotechnology has ultra-thin-film capability, which can be used to treat flexible, porous materials such as antimicrobial bandages.
  • silver ions can be incorporated in carrier particles - like zeolites - which can then be applied to the contact surface, preferably after it is treated by PECVD to provide a functional coating.
  • nanoparticles or ions of silver can be entrained in an airstream, conveyed into plasma enhanced chemical vapor deposition or similar apparatus, and driven into the contact surface or a surface coating on the contact surface, as by applying a DC bias to an electrode behind the contact surface relative to the source of nanoparticles.
  • the invention is believed to function as follows, although this theory of operation does not limit the invention, and any inaccuracy of this theory does not change the scope of the invention.
  • Silver ions are believed to work at the surface of a product through the controlled release of silver ions which attack microbes and inhibit their growth.
  • the silver ions exchange with other positive ions (often sodium) from the moisture in the environment, effecting a release of silver "on demand".
  • Silver ions are randomly oriented and distributed through the surface of a fiber, polymer or coating. In conditions that support bacterial growth, positive ions, in ambient moisture, exchange with silver ions. The exchanged silver ions are now available to control microbial growth. Silver ions attack multiple targets in the microbe to prevent it from growing to a destructive population. They are believed to fight cell growth in three ways:
  • Example 0 Basic Protocols for Forming and Coating Tubes and Syringe Barrels
  • Protocol for Forming COC Tube (used, e.g., in Examples 1, 19)
  • Cyclic olefin copolymer (COC) tubes of the shape and size commonly used as evacuated blood collection tubes (“COC tubes”) were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end.
  • Protocol for Forming PET Tube (used, e.g., in Examples 2, 4, 8, 9, 10)
  • PET tubes Polyethylene terephthalate (PET) tubes of the type commonly used as evacuated blood collection tubes (“PET tubes”) were injection molded in the same mold used for the Protocol for Forming COC Tube, having these dimensions: 75 mm length, 13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of about 7.25 cm and a closed, rounded end.
  • PET tubes Polyethylene terephthalate
  • the vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm).
  • the vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45).
  • the tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen 610 was a perforated copper foil material (K&S).
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone (“PEEK”) capillary (outside diameter, "OD” 1/16-inch (1.5-mm.), inside diameter, "ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m).
  • PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • HMDSO liquid hexamethyldisi
  • the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system. The pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • Pressure inside the tube was approximately 300 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 50 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 50 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 5 seconds until the RF power was terminated by the timer.
  • the plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed. The vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr). The tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • the vessel holder 50 was made from Delrin® acetal resin, available from E.I. du Pont de Nemours and Co., Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm).
  • the vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode (160).
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the tube used as the vessel 80 was inserted into the vessel holder 50 base sealing with Viton® O-rings 490, 504 (Viton® is a trademark of DuPont Performance Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube (FIG. 45).
  • the tube 80 was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen 610 was a perforated copper foil material (K&S).
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was 12 holes in the probe or counter electrode 108 along the length of the tube (three on each of four sides oriented 90 degrees from each other) and two holes in the aluminum cap that plugged the end of the gas delivery port 110.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port 110 (under process pressures) into the interior of the tube.
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Part # EW- 32661-34, Cole-Parmer Instrument Co., Barrington Illinois USA) for controllably flowing oxygen at 60 seem (or at the specific flow reported for a particular example) into the process and a polyether ether ketone (“PEEK”) capillary (outside diameter, "OD” 1/16-inch (1.5-mm.), inside diameter, "ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m).
  • PEEK capillary end was inserted into liquid hexamethyldisiloxane ("HMDSO," Alfa Aesar® Part Number L16970, NMR Grade, available from Johnson Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to the lower pressure in the tube during processing. The HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • HMDSO liquid hexamethyldisi
  • the gas stream (including the oxygen) was diverted to the pumping line when it was not flowing into the interior of the tube for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the tube.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the tube to be reduced to pressure(s) of less than 200 mTorr while the process gases were flowing at the indicated rates.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • Pressure inside the tube was approximately 270 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 39 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 39 Watts (or the specific amount reported for a particular example) and the reflected power was 0 Watts so that the applied power was delivered to the interior of the tube.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 7 seconds (or the specific time period reported for a particular example). Upon initiation of the RF power, a uniform plasma was established inside the interior of the tube. The plasma was maintained for the entire 7 seconds until the RF power was terminated by the timer. The plasma produced a silicon oxide coating of approximately 20 nm thickness (or the specific thickness reported in a particular example) on the interior of the tube contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the tube to atmospheric pressure (approximately 760 Torr).
  • the tube was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • Syringe barrels (“COC syringe barrels”), CV Holdings Part 11447, each having a 2.8 mL overall volume (excluding the Luer fitting) and a nominal 1 mL delivery volume or plunger displacement, Luer adapter type, were injection molded from Topas® 8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG, Frankfurt am Main, Germany, having these dimensions: about 51 mm overall length, 8.6 mm inner syringe barrel diameter and 1.27 mm wall thickness at the cylindrical portion, with an integral 9.5 millimeter length needle capillary Luer adapter molded on one end and two finger flanges molded near the other end.
  • COC cyclic olefin copolymer
  • An injection molded COC syringe barrel was interior coated with SiOx.
  • the apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel.
  • a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26), allowing the interior of the COC syringe barrel to be evacuated.
  • the vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the COC syringe barrel was inserted into the vessel holder 50, base sealing with an Viton® O- rings.
  • the COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
  • the probe or counter electrode 108 extended approximately 20 mm into the interior of the COC syringe barrel and was open at its end.
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gases, oxygen and
  • HMDSO hexamethyldisiloxane
  • the gas system was comprised of a Aalborg® GFC17 mass flow meter (Cole Parmer Part # EW-32661-34) for controllably flowing oxygen at 90 seem (or at the specific flow reported for a particular example) into the process and a PEEK capillary (OD 1/16-inch (3-mm) ID 0.004 inches (0.1 mm)) of length 49.5 inches (1.26 m).
  • the PEEK capillary end was inserted into liquid hexamethyldisiloxane (Alfa Aesar® Part Number L16970, NMR Grade).
  • the liquid HMDSO was pulled through the capillary due to the lower pressure in the COC syringe barrel during processing.
  • the HMDSO was then vaporized into a vapor at the exit of the capillary as it entered the low pressure region.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 150 mTorr while the process gases were flowing at the indicated rates.
  • a lower pumping pressure was achievable with the COC syringe barrel, as opposed to the tube, because the COC syringe barrel has a much smaller internal volume.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream oxygen and HMDSO vapor
  • the pressure inside the COC syringe barrel was approximately 200 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 8 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 30 Watts.
  • the RF power supply was connected to a COMDEL CPMX1000 auto match that matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 30 Watts (or whatever value is reported in a working example) and the reflected power was 0 Watts so that the power was delivered to the interior of the COC syringe barrel.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 5 seconds (or the specific time period reported for a particular example).
  • a uniform plasma was established inside the interior of the COC syringe barrel.
  • the plasma was maintained for the entire 5 seconds (or other coating time indicated in a specific example) until the RF power was terminated by the timer.
  • the plasma produced a silicon oxide coating of approximately 20 nm thickness (or the thickness reported in a specific example) on the interior of the COC syringe barrel contact surface.
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr).
  • the COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • COC syringe barrels as previously identified were interior coated with a lubricity layer.
  • the apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was modified to hold a COC syringe barrel with butt sealing at the base of the COC syringe barrel.
  • a cap was fabricated out of a stainless steel Luer fitting and a polypropylene cap that sealed the end of the COC syringe barrel (illustrated in FIG. 26).
  • the installation of a Buna-N O-ring onto the Luer fitting allowed a vacuum tight seal, allowing the interior of the COC syringe barrel to be evacuated.
  • the vessel holder 50 was made from Delrin® with an outside diameter of 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin® structure that allowed the device to move in and out of the electrode 160.
  • the electrode 160 was made from copper with a Delrin® shield.
  • the Delrin® shield was conformal around the outside of the copper electrode 160.
  • the electrode 160 measured approximately 3 inches (76 mm) high (inside) and was approximately 0.75 inches (19 mm) wide.
  • the COC syringe barrel was inserted into the vessel holder 50, base sealing with Viton® O-rings around the bottom of the finger flanges and lip of the COC syringe barrel.
  • the COC syringe barrel was carefully moved into the sealing position over the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter electrode 108 and pushed against a copper plasma screen.
  • the copper plasma screen was a perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringe barrel and was held in place by a abutment contact surface 494 that acted as a stop for the COC syringe barrel insertion. Two pieces of the copper mesh were fit snugly around the brass probe or counter electrode 108 insuring good electrical contact.
  • the probe or counter electrode 108 extended approximately 20mm (unless otherwise indicated) into the interior of the COC syringe barrel and was open at its end.
  • the brass probe or counter electrode 108 extended through a Swagelok® fitting located at the bottom of the vessel holder 50, extending through the vessel holder 50 base structure.
  • the brass probe or counter electrode 108 was grounded to the casing of the RF matching network.
  • the gas delivery port 110 was connected to a stainless steel assembly comprised of Swagelok® fittings incorporating a manual ball valve for venting, a thermocouple pressure gauge and a bypass valve connected to the vacuum pumping line.
  • the gas system was connected to the gas delivery port 110 allowing the process gas,
  • OCTS octamethylcyclotetrasiloxane
  • the gas system was comprised of a commercially available Horiba VC1310/SEF8240 OMCTS 10SC 4CR heated mass flow vaporization system that heated the OMCTS to about 100°C.
  • the Horiba system was connected to liquid octamethylcyclotetrasiloxane (Alfa Aesar® Part Number A12540, 98%) through a 1/8-inch (3-mm) outside diameter PFA tube with an inside diameter of 1/16 in (1.5 mm).
  • the OMCTS flow rate was set to 1.25 seem (or the specific organosilicon precursor flow reported for a particular example). To ensure no condensation of the vaporized OMCTS flow past this point, the gas stream was diverted to the pumping line when it was not flowing into the interior of the COC syringe barrel for processing via a Swagelok® 3-way valve.
  • the vacuum pump valve was opened to the vessel holder 50 and the interior of the COC syringe barrel.
  • An Alcatel rotary vane vacuum pump and blower comprised the vacuum pump system.
  • the pumping system allowed the interior of the COC syringe barrel to be reduced to pressure(s) of less than 100 mTorr while the process gases were flowing at the indicated rates. A lower pressure could be obtained in this instance, compared to the tube and previous COC syringe barrel examples, because the overall process gas flow rate is lower in this instance.
  • the vessel holder 50 assembly was moved into the electrode 160 assembly.
  • the gas stream (OMCTS vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way valve from the pumping line to the gas delivery port 110).
  • Pressure inside the COC syringe barrel was approximately 140 mTorr as measured by a capacitance manometer (MKS) installed on the pumping line near the valve that controlled the vacuum.
  • MKS capacitance manometer
  • the pressure inside the gas delivery port 110 and gas system was also measured with the thermocouple vacuum gauge that was connected to the gas system. This pressure was typically less than 6 Torr.
  • the RF power supply was turned on to its fixed power level.
  • a ENI ACG-6 600 Watt RF power supply was used (at 13.56 MHz) at a fixed power level of approximately 7.5 Watts (or other power level indicated in a specific example).
  • the RF power supply was connected to a COMDEL CPMX1000 auto match which matched the complex impedance of the plasma (to be created in the COC syringe barrel) to the 50 ohm output impedance of the ENI ACG-6 RF power supply.
  • the forward power was 7.5 Watts and the reflected power was 0 Watts so that 7.5 Watts of power (or a different power level delivered in a given example) was delivered to the interior of the COC syringe barrel.
  • the RF power supply was controlled by a laboratory timer and the power on time set to 10 seconds (or a different time stated in a given example).
  • the gas flow was diverted back to the vacuum line and the vacuum valve was closed.
  • the vent valve was then opened, returning the interior of the COC syringe barrel to atmospheric pressure (approximately 760 Torr).
  • the COC syringe barrel was then carefully removed from the vessel holder 50 assembly (after moving the vessel holder 50 assembly out of the electrode 160 assembly).
  • HMDSO hexamethyldisiloxane
  • O-Si organosilicon
  • COC cyclic olefin copolymer
  • OTR oxygen transmission rate
  • WVTR water vapor transmission rate
  • the uncoated COC tube had an OTR of 0.215 cc/tube/day.
  • Tubes A and B subjected to PECVD for 14 seconds had an average OTR of 0.0235 cc/tube/day.
  • Tube C subjected to PECVD for 7 seconds had an OTR of 0.026.
  • This result shows that the SiO x coating provided an OTR BIF over the uncoated tube of 8.3.
  • the SiO x barrier coating applied in 7 seconds reduced the oxygen transmission through the tube to less than one eighth of its value without the coating.
  • a series of syringe barrels were made according to the Protocol for Forming COC Syringe barrel.
  • the syringe barrels were either barrier coated with SiO x or not under the conditions reported in the Protocol for Coating COC Syringe barrel Interior with SiO x modified as indicated in Table 3.
  • OTR and WVTR samples of the syringe barrels were prepared by epoxy- sealing the open end of each syringe barrel to an aluminum adaptor. Additionally, the syringe barrel capillary ends were sealed with epoxy.
  • the syringe-adapter assemblies were tested for OTR or WVTR in the same manner as the PET tube samples, again using a MOCON® Oxtran 2/21 Oxygen Permeability Instrument and a MOCON® Permatran- W 3/31 Water Vapor Permeability Instrument. The results are reported in Table 3.
  • V.A PET tubes made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiO x were cut in half to expose the inner tube contact surface, which was then analyzed using X-ray photoelectron spectroscopy (XPS).
  • XPS X-ray photoelectron spectroscopy
  • V.A The XPS data was quantified using relative sensitivity factors and a model which assumes a homogeneous layer.
  • the analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
  • V.A. Table 5 provides the atomic ratios of the elements detected.
  • the analytical parameters used in for XPS are as follows:
  • V.A The Inventive Example has an Si/O ratio of 2.4 indicating an SiO x composition, with some residual carbon from incomplete oxidation of the coating. This analysis demonstrates the composition of an SiO x barrier layer applied to a polyethylene terephthalate tube according to the present invention.
  • V.A. Table 4 shows the thickness of the SiO x samples, determined using TEM according to the following method. Samples were prepared for Focused Ion Beam (FIB) cross- sectioning by coating the samples with a sputtered layer of platinum (50-100nm thick) using a K575X Emitech coating system. The coated samples were placed in an FEI FIB200 FIB system. An additional layer of platinum was FIB-deposited by injection of an organo-metallic gas while rastering the 30kV gallium ion beam over the area of interest. The area of interest for each sample was chosen to be a location half way down the length of the tube.
  • FIB Focused Ion Beam
  • Thin cross sections measuring approximately 15 ⁇ ("micrometers") long, 2 ⁇ wide and 15 ⁇ deep were extracted from the die contact surface using a proprietary in-situ FIB lift-out technique.
  • the cross sections were attached to a 200 mesh copper TEM grid using FIB-deposited platinum.
  • One or two windows in each section, measuring about 8 ⁇ wide, were thinned to electron transparency using the gallium ion beam of the FEI FIB.
  • V.C Cross-sectional image analysis of the prepared samples was performed utilizing a Transmission Electron Microscope (TEM). The imaging data was recorded digitally. [00484] The sample grids were transferred to a Hitachi HF2000 transmission electron microscope. Transmitted electron images were acquired at appropriate magnifications. The relevant instrument settings used during image acquisition are given below.
  • TEM Transmission Electron Microscope
  • V.A COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were treated using the Protocol for Coating COC Syringe Barrel Interior with SiO x> with the following variations. Three different modes of plasma generation were tested for coating syringe barrels such as 250 with SiO x films. V.A. In Mode 1, hollow cathode plasma ignition was generated in the gas inlet 310, restricted area 292 and processing vessel lumen 304, and ordinary or non-hollow-cathode plasma was generated in the remainder of the vessel lumen 300.
  • V.A The syringe barrels 250 were then exposed to a ruthenium oxide staining technique.
  • the stain was made from sodium hypochlorite bleach and Ru (III) chloride hydrate.
  • Ru (EI) chloride hydrate was put into a vial. 10ml bleach were added and mixed thoroughly until the Ru(III) chloride hydrate dissolved.
  • V.A Each syringe barrel was sealed with a plastic Luer seal and 3 drops of the staining mixture were added to each syringe barrel. The syringe barrels were then sealed with aluminum tape and allowed to sit for 30-40 minutes. In each set of syringe barrels tested, at least one uncoated syringe barrel was stained. The syringe barrels were stored with the restricted area 292 facing up.
  • V.A. The stain started to attack the uncoated (or poorly coated) areas within 0.25 hours of exposure;
  • V.A. 3 The best syringe barrel was produced by the test with no hollow cathode plasma ignition in either the gas inlet 310 or the restricted area 292. Only the restricted opening 294 was stained, most likely due to leaking of the stain; and
  • V.A Based on all of the above, we concluded: V.A. 1. Under the conditions of the test, hollow cathode plasma in either the gas inlet 310 or the restricted area 292 led to poor uniformity of the coating; and
  • V.A. 2 The best uniformity was achieved with no hollow cathode plasma in either the gas inlet 310 or the restricted area 292.
  • Tungsten 200-1000nm Tungsten 200-1000nm
  • a fiber optic reflection probe combination emitter/collector Ocean Optics QR400-7 SR/BX with approximately 3mm probe area
  • miniature detector Ocean Optics HR4000CG UV-NIR Spectrometer
  • software converting the spectrometer signal to a transmittance/wavelength graph on a laptop computer, an uncoated PET tube Becton Dickinson (Franklin Lakes, New Jersey, USA) Product No.
  • 366703 13x75 mm (no additives) is scanned (with the probe emitting and collecting light radially from the centerline of the tube, thus normal to the coated contact surface) both about the inner circumference of the tube and longitudinally along the inner wall of the tube, with the probe, with no observable interference pattern observed. Then a Becton Dickinson Product No. 366703 13x75 mm (no additives) SiO x plasma- coated BD 366703 tube is coated with a 20 nanometer thick Si0 2 coating as described in Protocol for Coating Tube Interior with SiO x. This tube is scanned in a similar manner as the uncoated tube. A clear interference pattern is observed with the coated tube, in which certain wavelengths were reinforced and others canceled in a periodic pattern, indicating the presence of a coating on the PET tube.
  • VIA The equipment used was a Xenon light source (Ocean Optics HL-2000-HP- FHSA - 20W output Halogen Lamp Source (185-2000nm)), an Integrating Sphere detector (Ocean Optics ISP-80-8-I) machined to accept a PET tube into its interior, and HR2000+ES Enhanced Sensitivity UV.VIS spectrometer, with light transmission source and light
  • receiver fiber optic sources QP600-2-UV-VIS - 600um Premium Optical FIBER, UV/VIS, 2m
  • signal conversion software SPECTRASUITE - Cross-platform Spectroscopy
  • An uncoated PET tube made according to the Protocol for Forming PET Tube was inserted onto a TEFZEL Tube Holder (Puck), and inserted into the integrating sphere. With the Spectrasuite software in absorbance mode, the absorption (at 615nm) was set to zero.
  • An SiOx coated tube made according to the Protocol for Forming PET Tube and coated according to the Protocol for Coating Tube Interior with SiOx was then mounted on the puck, inserted into the integrating sphere and the absorbance recorded at 615nm wavelength. The data is recorded in Table 16.
  • VIA VIA. These spectroscopic methods should not be considered limited by the mode of collection (for example, reflectance vs. transmittance vs. absorbance), the frequency or type of radiation applied, or other parameters.
  • FIG. 30, adapted from FIG. 15 of U.S. Patent 6,584,828, is a schematic view of a test set-up that was used in a working example for measuring outgassing through an SiO x barrier coating 348 applied according to the Protocol for Coating Tube Interior with SiO x on the interior of the wall 346 of a PET tube 358 made according to the Protocol for Forming PET Tube seated with a seal 360 on the upstream end of a Micro-Flow Technology measurement cell generally indicated at 362.
  • VLB VLB.
  • a vacuum pump 364 was connected to the downstream end of a commercially available measurement cell 362 (an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, ( ⁇ /min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time.
  • This equipment is supplied by ATC Inc.), and was configured to draw gas from the interior of the PET vessel 358 in the direction of the arrows through the measurement cell 362 for determination of the mass flow rate outgassed vapor into the vessel 358 from its walls.
  • VLB The measurement cell 362 shown and described schematically here was understood to work substantially as follows, though this information might deviate somewhat from the operation of the equipment actually used.
  • the cell 362 has a conical passage 368 through which the outgassed flow is directed.
  • the pressure is tapped at two longitudinally spaced lateral bores 370 and 372 along the passage 368 and fed respectively to the chambers 374 and 376 formed in part by the diaphragms 378 and 380.
  • the pressures accumulated in the respective chambers 374 and 376 deflect the respective diaphragms 378 and 380.
  • a bypass 386 can optionally be provided to speed up the initial pump-down by bypassing the measurement cell 362 until the desired vacuum level for carrying out the test is reached.
  • VLB The PET walls 350 of the vessels used in this test were on the order of 1 mm thick, and the coating 348 was on the order of 20 nm (nanometers) thick. Thus, the wall 350 to coating 348 thickness ratio was on the order of 50,000 : 1.
  • VLB To determine the flow rate through the measurement cell 362, including the vessel seal 360, 15 glass vessels substantially identical in size and construction to the vessel 358 were successively seated on the vessel seal 360, pumped down to an internal pressure of 1 Torr, then capacitance data was collected with the measurement cell 362 and converted to an
  • outgassing flow rate The test was carried out two times on each vessel. After the first run, the vacuum was released with nitrogen and the vessels were allowed recovery time to reach equilibrium before proceeding with the second run. Since a glass vessel is believed to have very little outgassing, and is essentially impermeable through its wall, this measurement is understood to be at least predominantly an indication of the amount of leakage of the vessel and connections within the measurement cell 362, and reflects little if any true outgassing or permeation. The results are in Table 7.
  • VLB The family of plots 390 in FIG. 31 shows the "outgas" flow rate, also in micrograms per minute, of individual tubes corresponding to the second run data in previously- mentioned Table 7. Since the flow rates for the plots do not increase substantially with time, and are much lower than the other flow rates shown, the flow rate is attributed to leakage.
  • VLB Table 8 and the family of plots 392 in FIG. 31 show similar data for uncoated tubes made according to the Protocol for Forming PET Tube.
  • VLB This data for uncoated tubes shows much larger flow rates: the increases are attributed to outgas flow of gases captured on or within the inner region of the vessel wall.
  • VLB VLB.
  • Table 9 and the families of plots 394 and 396 in FIG. 31 show similar data for an SiO x barrier coating 348 applied according to the Protocol for Coating PET Tube Interior with SiO x on the interior of the wall 346 of a PET tube made according to the Protocol for Forming PET Tube.
  • VLB The family of curves 394 for the SiO x coated, injection-molded PET tubes of this example shows that the SiO x coating acts as a barrier to limit outgassing from the PET vessel walls, since the flow rate is consistently lower in this test than for the uncoated PET tubes. (The SiO x coating itself is believed to outgas very little.) The separation between the curves 394 for the respective vessels indicates that this test is sensitive enough to distinguish slightly differing barrier efficacy of the SiO x coatings on different tubes.
  • VLB Referring to Tables 8 and 9 previously mentioned and FIG. 32, the data was analyzed statistically to find the mean and the values of the first and third standard deviations above and below the mean (average). These values are plotted in FIG. 32.
  • VLB This statistical analysis also shows the power of an outgassing measurement to very quickly and accurately analyze the barrier efficacy of nano-thickness barrier coatings and to distinguish coated tubes from uncoated tubes (which are believed to be indistinguishable using the human senses at the present coating thickness).
  • This data shows no overlap of the data to a level of certainty exceeding 6 ⁇ (six-sigma).
  • VLB VLB
  • the wetting tension method is a modification of the method described in ASTM D 2578. Wetting tension is a specific measure for the hydrophobicity or hydrophilicity of a contact surface. This method uses standard wetting tension solutions (called dyne solutions) to determine the solution that comes nearest to wetting a plastic film contact surface for exactly two seconds. This is the film's wetting tension.
  • VILA.1.a.ii The procedure utilized is varied from ASTM D 2578 in that the substrates are not flat plastic films, but are tubes made according to the Protocol for Forming PET Tube and (except for controls) coated according to the Protocol for Coating Tube Interior with Hydrophobic layer.
  • a silicone coated glass syringe (Becton Dickinson Hypak® PRTC glass prefillable syringe with Luer-lok® tip) (1 mL) was also tested. The results of this test are listed in Table 10.
  • VH.A. l.a.ii Surprisingly, plasma coating of uncoated PET tubes (40 dynes/cm) can achieve either higher (more hydrophilic) or lower (more hydrophobic) energy contact surfaces using the same hexamethyldisiloxane (HMDSO) feed gas, by varying the plasma process conditions.
  • a thin (approximately 20-40 nanometers) SiO x coating made according to the Protocol for Coating Tube Interior with SiO x (data not shown in the tables) provides similar wettability as hydrophilic bulk glass substrates.
  • a thin (less than about 100 nanometers) hydrophobic layer made according to the Protocol for Coating Tube Interior with Hydrophobic layer provides similar non- wettability as hydrophobic silicone fluids (data not shown in the tables).
  • PET tubes made according to the Protocol for Forming PET Tube, closed with the same type of Hemogard® system red stopper and uncolored guard [internal control];
  • Water volume draw change determinations were made by (a) removing 3-5 samples at increasing time intervals, (b) permitting water to draw into the evacuated tubes through a 20 gauge blood collection adaptor from a one liter plastic bottle reservoir, (c) and measuring the mass change before and after water draw.
  • VH.B.l.a The jig was installed on the Dillon Test Stand. The platform probe movement was adjusted to 6 in/min (2.5 mm/sec) and upper and lower stop locations were set. The stop locations were verified using an empty syringe and barrel. The commercial saline- filled syringes were labeled, the plungers were removed, and the saline solution was drained via the open ends of the syringe barrels for re-use. Extra plungers were obtained in the same manner for use with the COC and glass barrels.
  • VH.B.l.a Syringe plungers were inserted into the COC syringe barrels so that the second horizontal molding point of each plunger was even with the syringe barrel lip (about 10 mm from the tip end).
  • the test syringes were filled via the capillary end with 2-3 milliliters of saline solution, with the capillary end uppermost. The sides of the syringe were tapped to remove any large air bubbles at the plunger/ fluid interface and along the walls, and any air bubbles were carefully pushed out of the syringe while maintaining the plunger in its vertical orientation.
  • VH.B.l.a Each filled syringe barrel/plunger assembly was installed into the syringe jig. The test was initiated by pressing the down switch on the test stand to advance the moving metal hammer toward the plunger. When the moving metal hammer was within 5mm of contacting the top of the plunger, the data button on the Dillon module was repeatedly tapped to record the force at the time of each data button depression, from before initial contact with the syringe plunger until the plunger was stopped by contact with the front wall of the syringe barrel.
  • VH.B.l.a All benchmark and coated syringe barrels were run with five replicates (using a new plunger and barrel for each replicate).
  • VH.B.l.a COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were coated with an OMCTS lubricity layer according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer, assembled and filled with saline, and tested as described above in this Example for lubricity layers.
  • the polypropylene chamber used per the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer allowed the OMCTS vapor (and oxygen, if added - see Table 13) to flow through the syringe barrel and through the syringe capillary into the polypropylene chamber (although a lubricity layer can not be needed in the capillary section of the syringe in this instance).
  • OMCTS vapor and oxygen, if added - see Table 13
  • Table 13 Several different coating conditions were tested, as shown in previously mentioned Table 13. All of the depositions were completed on COC syringe barrels from the same production batch.
  • VH.B.l.a The samples were created by coating COC syringe barrels according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer.
  • VH.B.l.a The force required to expel a 0.9 percent saline payload from a syringe through a capillary opening using a plastic plunger was determined for inner wall-coated syringes.
  • VH.B.l.a Three types of COC syringe barrels made according to the Protocol for Forming COC Syringe barrel were tested: one type having no internal coating [Uncoated Control], another type with a hexamethyldisiloxane (HMDSO)-based plasma coated internal wall coating [HMDSO Control] according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, and a third type with an octamethylcyclotetrasiloxane [OMCTS - Inventive Example] -based plasma coated internal wall coating applied according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer.
  • Fresh plastic plungers with elastomeric tips taken from BD Product Becton-Dickinson Product No. 306507 were used for all examples. Saline from Product No. 306507 was also used.
  • VH.B.l.a The plasma coating method and apparatus for coating the syringe barrel inner walls is described in other experimental sections of this application.
  • the specific coating parameters for the HMDSO-based and OMCTS-based coatings are listed in the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating, the Protocol for Coating COC Syringe barrel Interior with OMCTS Lubricity layer, and Table 14.
  • VH.B.l.a The plunger is inserted into the syringe barrel to about 10 millimeters, followed by vertical filling of the experimental syringe through the open syringe capillary with a separate saline-filled syringe/needle system.
  • the syringe is tapped to permit any air bubbles adhering to the inner walls to release and rise through the capillary opening.
  • VH.B.l.a The filled experimental syringe barrel/plunger assembly is placed vertically into a home-made hollow metal jig, the syringe assembly being supported on the jig at the finger flanges.
  • the jig has a drain tube at the base and is mounted on Dillon Test Stand with Advanced Force Gauge (Model AFG-50N).
  • the test stand has a metal hammer, moving vertically downward at a rate of six inches (152 millimeters) per minute. The metal hammer contacts the extended plunger expelling the saline solution through the capillary. Once the plunger has contacted the syringe barrel/capillary interface the experiment is stopped.
  • VH.B.l.a During downward movement of the metal hammer/extended plunger, resistance force imparted on the hammer as measured on the Force Gauge is recorded on an electronic spreadsheet. From the spreadsheet data, the maximum force for each experiment is identified.
  • VH.B.l.a Table 14 lists for each Example the Maximum Force average from replicate coated COC syringe barrels and the Normalized Maximum Force as determined by division of the coated syringe barrel Maximum Force average by the uncoated Maximum Force average.
  • VII.B.1.a The data indicates all OMCTS-based inner wall plasma coated COC syringe barrels (Inventive Examples C,E,F,G,H) demonstrate much lower plunger sliding force than uncoated COC syringe barrels (uncoated Control Examples A & D) and surprisingly, also much lower plunger sliding force than HMDSO-based inner wall plasma coated COC syringe barrels (HMDSO control Example B).
  • an OMCTS-based coating over a silicon oxide (SiO x ) gas barrier coating maintains excellent low plunger sliding force (Inventive Example F).
  • a COC syringe barrel formed according to the Protocol for Forming COC Syringe barrel is sealed at both ends with disposable closures.
  • the capped COC syringe barrel is passed through a bath of Daran® 8100 Saran Latex (Owensboro Specialty Plastics). This latex contains five percent isopropyl alcohol to reduce the contact surface tension of the composition to 32 dynes/cm).
  • the latex composition completely wets the exterior of the COC syringe barrel.
  • the coated COC syringe barrel is exposed to a heating schedule comprising 275°F (135°C) for 25 seconds (latex coalescence) and 122°F (50°C) for four hours (finish cure) in respective forced air ovens.
  • the resulting PVdC film is 1/10 mil (2.5 microns) thick.
  • the COC syringe barrel and PVdC-COC laminate COC syringe barrel are measured for OTR and WVTR using a MOCON brand Oxtran 2/21 Oxygen Permeability Instrument and Permatran- W 3/31 Water Vapor Permeability Instrument, respectively.
  • COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or coated with HMDSO according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating were provided.
  • the atomic compositions of the coatings derived from OMCTS or HMDSO were characterized using X-Ray Photoelectron Spectroscopy (XPS).
  • XPS data is quantified using relative sensitivity factors and a model that assumes a homogeneous layer.
  • the analysis volume is the product of the analysis area (spot size or aperture size) and the depth of information. Photoelectrons are generated within the X-ray penetration depth (typically many microns), but only the photoelectrons within the top three photoelectron escape depths are detected. Escape depths are on the order of 15-35 A, which leads to an analysis depth of -50-100 A. Typically, 95% of the signal originates from within this depth.
  • VII.B.4 Table 17 provides the atomic concentrations of the elements detected. XPS does not detect hydrogen or helium. Values given are normalized to 100 percent using the elements detected. Detection limits are approximately 0.05 to 1.0 atomic percent. [00544] VII.B.4. From the coating composition results and calculated starting monomer precursor elemental percent in Table 17, while the carbon atom percent of the HMDSO-based coating is decreased relative to starting HMDSO monomer carbon atom percent (54.1% down to 44.4%), surprisingly the OMCTS-based coating carbon atom percent is increased relative to the OMCTS monomer carbon atom percent (34.8% up to 48.4%), an increase of 39 atomic %, calculated as follows:
  • COC syringe barrel samples made according to the Protocol for Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity layer) or with HMDSO (according to the Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating) were provided.
  • Outgassing gas chromatography/mass spectroscopy (GC/MS) analysis was used to measure the volatile components released from the OMCTS or HMDSO coatings.
  • MSD Mass Selective Detector
  • HMDSO-based compositions outgassed trimethylsilanol [(Me) 3 SiOH] but outgassed no measured higher oligomers containing repeating -(Me) 2 SiO- moieties
  • OMCTS-based compositions outgassed no measured trimethylsilanol [(Me ⁇ SiOH] but outgassed higher oligomers containing repeating -(Me) 2 SiO- moieties. It is contemplated that this test can be useful for differentiating HMDSO-based coatings from OMCTS-based coatings.
  • OMCTS is contemplated to react by ring opening to form a diradical having repeating -(Me) 2 SiO- moieties which are already oligomers, and can condense to form higher oligomers.
  • HMDSO is contemplated to react by cleaving at one O-Si bond, leaving one fragment containing a single O-Si bond that recondenses as (Me ⁇ SiOH and the other fragment containing no O-Si bond that recondenses as [(Me) 3 Si] 2 .
  • the cyclic nature of OMCTS is believed to result in ring opening and condensation of these ring-opened moieties with outgassing of higher MW oligomers (26 ng/test).
  • HMDSO-based coatings are believed not to provide any higher oligomers, based on the relatively low-molecular- weight fragments from HMDSO.
  • HMDSO-based and OMCTS-based coatings there is a fundamental difference in reaction mechanism in the formation of the respective HMDSO-based and OMCTS-based coatings.
  • HMDSO fragments can more easily nucleate or react to form dense nanoparticles which then deposit on the contact surface and react further on the contact surface, whereas OMCTS is much less likely to form dense gas phase nanoparticles.
  • OMCTS reactive species are much more likely to condense on the contact surface in a form much more similar to the original OMCTS monomer, resulting in an overall less dense coating.
  • COC tubes were made according to the Protocol for Forming COC Tube. Some of the tubes were provided with an interior barrier coating of SiOx according to the Protocol for Coating Tube Interior with SiO x , and other COC tubes were uncoated. Commercial glass blood collection Becton Dickinson 13 x 75 mm tubes having similar dimensions were also provided as above. The tubes were stored for about 15 minutes in a room containing ambient air at 45% relative humidity and 70 ° F (21 ° C), and the following testing was done at the same ambient relative humidity.
  • Example 8 an Intelligent Gas Leak System with Leak Test Instrument Model ME2, with second generation IMFS sensor, ( ⁇ /min full range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of reading, at calibrated range, employing the Leak-Tek Program for automatic data acquisition (with PC) and signatures/plots of leak flow vs. time).
  • each tube was subjected to a 22- second bulk moisture degassing step at a pressure of 1 mm Hg, was pressurized with nitrogen gas for 2 seconds (to 760 millimeters Hg), then the nitrogen gas was pumped down and the microflow measurement step was carried out for about one minute at 1 millimeter Hg pressure.

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Abstract

La présente invention concerne un procédé de fabrication d'un dispositif médical antimicrobien. La présente invention concerne un dispositif médical ou un matériau ou une partie de celui-ci comprenant une surface de contact. Un premier traitement de SiOx, SiOxCy, ou SiNxCy est appliqué sur la surface de contact. Avant ou après le premier traitement, un deuxième traitement antimicrobien efficace est appliqué sur la surface de contact. Le deuxième traitement est un traitement d'un métal choisi parmi l'argent (préféré), l'or, le platine, le cuivre, le tantale, le titane, le zirconium, l'hafnium, ou le zinc, ou un composé du métal, appliqué sur la surface de contact avec son premier traitement. La présente invention concerne en outre des dispositifs médicaux ou leurs composants fabriqués selon le procédé ci-dessus.
PCT/US2014/032919 2013-04-04 2014-04-04 Traitement antimicrobien de surfaces de dispositif médical WO2014165727A1 (fr)

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CN108175397A (zh) * 2017-11-30 2018-06-19 杭州欢乐飞机器人科技股份有限公司 一种人体测压用自动手爪装置
EP3490497A4 (fr) * 2016-07-26 2020-03-25 Singapore Health Services Pte Ltd Cylindre optique et procédé de traitement de surface de celui-ci
CN114073805A (zh) * 2021-11-03 2022-02-22 四川大学华西医院 一种可扩张尿道的泌尿外科尿道麻醉喷药器
CN114231389A (zh) * 2021-12-21 2022-03-25 四川大学华西医院 一种恒河猴耳蜗膜迷路组织细胞无损提取装置及使用方法
TWI761865B (zh) * 2020-06-19 2022-04-21 許軒杰 具有自動殺菌與保護功能之裝置
US11635148B2 (en) 2019-12-27 2023-04-25 Horizon Healthcare LLC Tube clamp
US11674617B2 (en) 2019-12-27 2023-06-13 Horizon Healthcare LLC Tube lock
CN118169049A (zh) * 2024-05-14 2024-06-11 济南市第三人民医院 一种慢性病食疗食品的安全快速检测设备

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3490497A4 (fr) * 2016-07-26 2020-03-25 Singapore Health Services Pte Ltd Cylindre optique et procédé de traitement de surface de celui-ci
CN108175397A (zh) * 2017-11-30 2018-06-19 杭州欢乐飞机器人科技股份有限公司 一种人体测压用自动手爪装置
CN108175397B (zh) * 2017-11-30 2023-12-15 深圳市富惠阳电子科技有限公司 一种人体测压用自动手爪装置
US11635148B2 (en) 2019-12-27 2023-04-25 Horizon Healthcare LLC Tube clamp
US11674617B2 (en) 2019-12-27 2023-06-13 Horizon Healthcare LLC Tube lock
TWI761865B (zh) * 2020-06-19 2022-04-21 許軒杰 具有自動殺菌與保護功能之裝置
CN114073805A (zh) * 2021-11-03 2022-02-22 四川大学华西医院 一种可扩张尿道的泌尿外科尿道麻醉喷药器
CN114231389A (zh) * 2021-12-21 2022-03-25 四川大学华西医院 一种恒河猴耳蜗膜迷路组织细胞无损提取装置及使用方法
CN118169049A (zh) * 2024-05-14 2024-06-11 济南市第三人民医院 一种慢性病食疗食品的安全快速检测设备

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