# Patent

## Title
Method and apparatus for detecting rapid barrier coating integrity characteristics

## Abstract

An apparatus and methods for testing the integrity of a barrier coating on a vessel. An off gas test fixture includes a face seal positioned about an opening of the vessel. A side seal is positioned about a portion of the vessel's wall and separated from the face seal by a space. Additionally, a cover may be secured to the fixture that encompasses an interface portion of the fixture and the vessel. Before and/or during testing, gas in the space between the side and face seals may be evacuated, as well as gas present in an interior area of the vessel. The vessel may be exposed to test gas(es) that is soluble by the plastic material of the vessel before and/or after being secured to the fixture. During testing, test gas(es) desorbed by the vessel may be evacuated, with the molecular flow being measured using a mass extraction unit.

## Background
This application incorporates by reference the entire specification, claims, and drawings of U.S. Ser. No. 12/779,007, filed May 12, 2010, and U.S. Provisional Ser. No. 61/413,355, filed Nov. 12, 2012.
The present invention relates to the technical field of fabrication of coated vessels for storing pharmaceutical drugs, biologically active compounds or blood. For example, the invention relates to a method and apparatus for testing the integrity of a barrier coating that has been applied to an interior or exterior of a vessel.
The present disclosure also relates to improved methods for processing vessels, for example testing the barrier coating integrity of vessels used for venipuncture and other medical sample collection, pharmaceutical preparation storage and delivery, and other purposes. Such vessels are used in large numbers for these purposes, and must be relatively economical to manufacture and yet highly reliable in storage and use.
BACKGROUND OF THE INVENTION
Evacuated blood collection tubes are used for drawing blood from a patient for medical analysis. The tubes are sold evacuated. The patient's blood is communicated to the interior of a tube by inserting one end of a double-ended hypodermic needle into the patient's blood vessel and impaling the closure of the evacuated blood collection tube on the other end of the double-ended needle. The vacuum in the evacuated blood collection tube draws the blood (or more precisely, the blood pressure of the patient pushes the blood) through the needle into the evacuated blood collection tube, increasing the pressure within the tube and thus decreasing the pressure difference causing the blood to flow. The blood flow typically continues until the tube is removed from the needle or the pressure difference is too small to support flow.
Evacuated blood collection tubes should have a substantial shelf life to facilitate efficient and convenient distribution and storage of the tubes prior to use. For example, a one-year shelf life is desirable, and progressively longer shelf lives, such as 18 months, 24 months, or 36 months, are also desired in some instances. The tube desirably remains essentially fully evacuated, at least to the degree necessary to draw enough blood for analysis (a common standard is that the tube retains at least 90% of the original draw volume), for the full shelf life, with very few (optimally no) defective tubes being provided.
A defective tube is likely to cause the phlebotomist using the tube to fail to draw sufficient blood. The phlebotomist might then need to obtain and use one or more additional tubes to obtain an adequate blood sample.
Parenteral containers are designed to store pharmaceutical drugs for 2-3 years prior to use. These containers include: vials, cartridges, ampoules and pre-filled syringes. Prefilled syringes are commonly prepared and sold so the syringe does not need to be filled before use. The syringe can be prefilled with saline solution, a dye for injection, or a pharmaceutically active preparation, for some examples.
Commonly, the prefilled syringe is capped at the distal end, as with a cap, and is closed at the proximal end by its drawn plunger. The prefilled syringe can be wrapped in a sterile package before use. To use the prefilled syringe, the packaging and cap are removed, optionally a hypodermic needle or another delivery conduit is attached to the distal end of the barrel, the delivery conduit or syringe is moved to a use position (such as by inserting the hypodermic needle into a patient's blood vessel or into apparatus to be rinsed with the contents of the syringe), and the plunger is advanced in the barrel to inject the contents of the barrel.
One important consideration in manufacturing pre-filled syringes is that the contents of the syringe desirably will have a substantial shelf life, during which it is important to isolate the material filling the syringe from the barrel wall containing it, to avoid leaching material from the barrel into the prefilled contents or vice versa.
Since many of these vessels are inexpensive and used in large quantities, for certain applications it will be useful to reliably obtain the necessary shelf life without increasing the manufacturing cost to a prohibitive level. It is also desirable for certain applications to move away from glass vessels, which can break and are expensive to manufacture, in favor of plastic vessels which are rarely broken in normal use (and if broken do not form sharp shards from remnants of the vessel, like a glass tube would). Glass vessels have been favored because glass is more gas tight and inert to pre-filled contents than untreated plastics. Also, due to its traditional use, glass is well accepted, as it is known to be relatively innocuous when contacted with medical samples or pharmaceutical preparations and the like.
To increase the shelf life of such plastic vessels, a barrier coating may be applied to the vessel that is configured to inhibit at least oxygen from the ambient environment outside of the vessel from entering into the interior area of the vessel. Yet, permeation testing the integrity of such coatings is time consuming, taking as little as 24 hours to upwards of 21 days depending on the thickness and barrier properties of the container/coating system. For example, currently, testing of barrier coating integrity may involve the relatively long process of Oxygen Transmission Rate (OTR). The OTR is a measure of oxygen permeation. Typical instruments that perform OTR testing include Mocon and Oxysense. However, such testing may take 7-14 days before the results of the testing, and the integrity of the barrier coating of the particular sample being tested, can be assessed.
Additionally, due to the sensitive nature of testing barrier coating integrity, current testing methods encounter challenges relating to the interface between the measurement device and the vessel. Moreover, this interface may be configured in such a way that allows for the undesirable flow of gases outside of the vessel into the measuring device, which thereby contributes to the recorded gas flow measurements, and thereby adversely impacts the accuracy of the test results. In Mocon-Oxtran type permeation measurement, the test article must be destructively glued to a support fixture. In the Oxysense measurement, an oxygen-sensitive adhesive tab must be affixed to the inside wall of the article It would be desirable to enable measurement in a non-destructive mode.
A non-exhaustive list of patents of possible relevance includes U.S. Pat. Nos. 6,068,884 and 4,844,986 and U.S. Published Applications 20060046006 and 20040267194.
SUMMARY OF THE INVENTION
An aspect of the invention is an off gas test fixture for testing the barrier coating integrity of a vessel, the vessel having at least one opening. The off gas test fixture includes an interface portion having an upper surface and a vertical wall. The upper surface is configured to abut against a top portion of the vessel adjacent to the opening. Additionally, the upper surface includes a face seal configured to provide a first seal about the opening when the vessel is secured to the off gas test fixture. The vertical wall includes a recess that is configured to house a side seal. The side seal is configured to provide a second seal between a portion of the wall of the vessel and the interface portion. The off gas test fixture further includes a vacuum line that is in communication with a space separating the first and second seals. The vacuum line is configured to be operably connected to a vacuum to evacuate gas from the space when the vessel is secured to the off gas test fixture.
Another aspect of the invention is a method for testing the barrier coating integrity of a vessel having at least one opening and a barrier coating. The method optionally includes exposing the vessel to a test gas. Further, a top portion of the vessel is securely engaged against an upper surface of an interface portion of an off gas test fixture. The engagement between the top portion of the vessel and the upper surface of the interface portion is sealed to provide a first gas seal. Additionally, an area between a portion of the wall of the vessel and the interface portion is also sealed to provide a second gas seal. The second gas seal is positioned to provide a space between the first gas seal and the second gas seal. Further, gas in the space between the first and second gas seals is evacuated. A vacuum is applied to the vessel to remove the test gas that had been absorbed by, or permeated into, the vessel. Additionally, test gas evacuated from the interior area is measured to determine the integrity of the barrier coating.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a front perspective view of an off gas test fixture with a cover shown as being partially transparent for at least purposes of illustration.
FIG. 2 illustrates a side partial cross sectional view of the off gas test fixture shown in FIG. 1.
FIG. 3 illustrates a cross sectional view of a portion of the off gas test fixture shown in FIG. 2.
FIG. 4 illustrates a process flow sheet illustrating a process for testing a sample in the off gas test fixture.
FIG. 5 illustrates a plot of molecular flow measured using a mass extraction unit for vessels having different degrees of barrier coating integrity.
FIG. 6 illustrates a plot of molecular flow measured using a mass extraction unit for vessels having different degrees of barrier coating integrity.



The following reference characters are used in the drawing figures:













1000
Off gas test fixture


1001
Base


1002
Vessel


1003
Opening


1004
Interior area


1005
Wall


1006
Bracket


1007
Interior surface


1008
Compression member


1010
Bottom portion


1012
Top portion


1013
Interface portion


1014
Passageway


1015
Face seal


1016
Upper surface


1017
Groove


1018
Side seal


1019
Vertical wall


1020
Recess


1022
Nut


1024
Vacuum line


1025
Release valve


1026
Upper portion


1028
Outer portion


1030
Connector


1032
Cover


1033
Top


1034
Clamp


1035
Sidewall


1036
Inner area


1037
Seal


1038
Extension


1040
Connector


1042
Vacuum port


1100
Evacuate article


1110
Expose article to



permeable gas


1120
Evacuate article


1130
Measure response









DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will now be described more fully with reference to the accompanying drawings, in which several embodiments are shown. This invention can, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth here. Rather, these embodiments are examples of the invention, which has the full scope indicated by the language of the claims. Like numbers refer to like or corresponding elements throughout.
Definition Section
In the context of the present invention, the following definitions and abbreviations are used:
Words such as “vertical” “horizontal,” “top,” and “bottom” designate directions in the drawings to which reference is made. This terminology includes the words specifically noted above, derivatives thereof, and words of similar import. This terminology is provided only for convenience in showing the relative orientation of the illustrated embodiment, and does not limit the scope of the claims.
The term “at least” in the context of the present invention means “equal or more” than the integer following the term. The word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality unless indicated otherwise.
“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.
A “vessel” in the context of the present invention can be any type of vessel with at least one opening and a wall defining an interior surface. The term “at least” in the context of the present invention means “equal or more” than the integer following the term. Thus, 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 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 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 having a substantially cylindrical wall adjacent to at least one of its open ends being preferred. Generally, the interior wall of the vessel 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) are contemplated.
FIGS. 1 and 2 illustrate an off gas test fixture 1000 for testing of the integrity of a barrier coating or coating on a substrate. Moreover, the off gas test fixture 1000 illustrated in FIGS. 1 and 2 may be employed in barrier coating integrity tests and/or testing of gas absorption and/or permeation, as discussed below, that may be completed in less than one hour, and preferably in 30 minutes or less. A vessel 1002 may be secured to a base 1001 of the off gas test fixture 1000 by a clamp and/or bracket 1006, for example, which assists in maintaining the vessel 1002 in a generally vertical position. The vessel 1002 includes an opening 1003 and a wall 1005 that generally define an interior surface 1007 and an interior area 1004 of the vessel 1002. A barrier coating, such as, for example, a SiOx coating, may be applied to at least the interior surface 1007 of the vessel 1002.
The bracket 1006 may be operably secured to the base 1001, such as, for example, by a weld or through the use of mechanical fasteners, including, for example, bolts screws, nuts, among others. According to certain embodiments, the bracket 1006 is configured to secure the vessel 1002 to the base 1001. However, according to other embodiments, the bracket 1006 may provide a location for the attachment of a releasable clamping, fastening, or compression member or mechanism that is used to secure the vessel 1002 to the off gas test fixture 1000. For example, as shown in FIGS. 1 and 2, the bracket 1006 may have an internal threaded aperture that is configured for a threaded engagement with the external thread of a compression member 1008. According to such an embodiment, as the compression member 1008 is tightened, the compression member 1008 may protrude through aperture and engage a bottom portion 1010 of the vessel 1002. The compression member 1008 may continue to be tightened to push a top portion 1012 of the vessel 1002 against the base 1001 until the vessel 1002 is relatively firmly secured in a generally vertical position between the base 1001 and the compression member 1008.
The base 1001 may include an interface portion 1013 that includes a passageway 1014 that is in communication with the opening 1003 of the vessel 1002 when the vessel 1002 is secured to the base 1001. The interface portion 1013 also includes a face seal 1015 that may be positioned about an upper surface 1016 of the base 1001. For example, according to certain embodiments, the face seal 1015 may be an O-ring that is secured in a groove 1017 in the upper surface 1016. The groove 1017 may have a variety of different configurations, including being generally trapezoidal, as shown for example in FIG. 3. Additionally, the face seal 1015 is positioned to abut against at least a portion of the top portion 1012 of the vessel 1002 about the opening 1003 when the vessel 1002 is secured to the off gas test fixture 1000 to provide a gas seal that prevents ambient air from passing into the vessel 1002.
The interface portion 1013 also includes a side seal 1018 that is positioned to abut against a portion of the outer surface of the wall 1005 of the vessel 1002 and at least a portion of the interface portion 1013. For example, the interface portion 1013 may include a vertical wall 1019 that encompasses at least a portion of the upper surface 1016. The vertical wall 1019 may include a recess 1020 that is configured to receive the placement of the side seal 1018. According to certain embodiments, after the vessel 1002 is at least partially secured to the off gas test fixture 1000, a nut 1022, such as a seal compression nut, may be secured to the interface portion 1013, such as, for example, via a threading engagement with the vertical wall 1019. The nut 1022 may be secured to the interface portion 1013 in a manner that compresses the side seal 1018 into a sealing engagement between a portion of the outer surface of the wall 1005 of the vessel 1002 and at least a portion of the interface portion 1013. Such a seal 1018 may be intended to prevent or minimize ambient air from passing beyond the seal 1018 toward and/or through the opening 1003 of the vessel 1002. Although FIGS. 1-3 illustrate the nut 1022 has having a separate upper portion 1026 and outer portion 1028, according to certain embodiments, the upper and outer portions 1026, 1028 may be part of the same unitary construction.
The interface portion 1013 also includes one or more vacuum lines 1024 that are in communication with the area or space between the face and side seals 1015, 1018 when the vessel 1002 is secured to the off gas test fixture 1000. At least one end of the vacuum line 1024 is operably connected, such as by a connector 1030, to a vacuum that is configured to remove air or other gases that are trapped in, or that enter into, the space between the face and side seals 1015, 1018. Such a vacuum may further prevent the leakage of gas into the vessel 1002 and/or passageway 1014 that may otherwise adversely impact the accuracy of testing conducted on integrity of the barrier coating. Additionally, according to certain embodiments, another end of the vacuum lines 1024 may be operably connected to a release valve or gas supply that allows gas to enter into the space between the seals 1015, 1018 when testing is completed to release the vacuum created between the seals 1015, 1018, and thereby increase the ease of removing the vessel 1002 from the off gas test fixture 1000.
The off gas test fixture 1000 may also include a cover 1032 that may encompass an area around the vessel 1002 and interface portion 1013, and which is seated upon the base 1001. According to certain embodiments, the cover 1032 may include a top 1033 and sidewall 1035 that define an inner area 1036. The cover 1032 may be secured to the base 1001 in a number of different fashions, including, for example, through the use of mechanical fasteners, such as, bolts, nuts, screws, and/or pins, among others. According to certain embodiments, the cover 1032 includes an extension 1038 that extends from the sidewall 1035. The extension 1038 may assist in securing the cover 1032 to the base 1001. For example, the extension 1038 may be configured to provide an area for engagement by one or more clamps 1034 that secure the cover 1032 to the base 1001. Additionally, as shown in FIG. 2, a seal 1037 may be positioned between a portion of the cover 1032, such as beneath the extension 1038, and the base 1001 that, when the cover 1032 is secured to the base 1001, prevents ambient air from entering into the inner area 1036 and/or prevents gases inside the inner area 1036 from leaking through the interface between the cover 1032 and the base 1001.
Additionally, a connector 1040 may be attached to the cover 1032, such as at the top 1033 or sidewall 1035. The connector may include a first end and a second end, the first end being operably connected to hosing or tubing that delivers and/or removes gases to/from the inner area 1036. The second end of the connector 1040 may be in communication with the inner area such that gases delivered to the connector may pass into the inner area 1036. Alternatively, rather than being connected to the cover, the connector 1040 may be operably connected to the base 1001 to assist in the delivery of gases to the inner area 1036 when the cover 1032 is secured to the base 1001.
The use of the seals 1015, 1018, as well as the removal of gases from the space between the seals 1015, 1018 via a vacuum, provides a test fixture configuration that isolates the interface between the vessel and the measurement device. Such isolation permits a separate measurement of the integrity of the barrier coating on the interior surface 1007 of the vessel 1002.
FIG. 4 illustrates a process flow sheet illustrating a process for testing a sample in the off gas test fixture 1000. As shown in FIG. 4, after the vessel 1002 has been secured to the off gas test fixture 1000, at step 1100, gases in the interior area 1004 may be evacuated, such as, for example, through the passageway 1014. The passageway 1014 may be operably connected to a vacuum port 1042 of a measurement device, such as, for example, a mass extraction unit, such as, for example, a commercially available Intelligent Gas Leak System with Leak Test Instrument Model ME2, integrated with a 0-2 μg/min sensor supplied by ATC Inc. Alternatively, rather than having the vacuum port 1042 indirectly in communication with the opening 1003 of the vessel 1002 via the passageway 1014, according to certain embodiments the base 1001 may be configured such that the vacuum port 1042 is in direct communication with the opening 1003. Additionally, at step 1100, gases in the space between the face seal 1015 and side seal 1018 may be evacuated, such as through the vacuum line 1024.
After gases in the interior area 1004 have been evacuated, at step 1110, the vessel 1002 may be exposed to test gas(es) that may be soluble, absorbed, adsorbed or permeable in or on a surface of the molded material of the wall 1005 of the vessel 1002. Typically, the test gas(es) is/are selected based on the type of plastic that is used to mold the vessel 1002. Moreover, the test gas may be required to be soluble (diffuse) into the plastic of the vessel 1002 without the barrier coating applied. For example, carbon dioxide gas is soluble in cyclic olefin polymer (COP) and cyclic olefin co-polymer (COC) materials. Accordingly, during testing, the vessel 1002 in the test fixture 1001 may be exposed to one or more test gases that may permeate through or be absorbed by the COP or COC plastic wall 1005 of the vessel 1002, such as, for example, carbon dioxide (CO2) and/or Helium (He) at a pressure and for a period of time that promotes such permeation and/or absorption.
However, for some plastics, such as PET for example, water vapor is soluble in PET, and therefore a discrete test gas may not be required. Yet, although such situations may not require a discrete test gas, those situations may require a controlled relative humidity so that the solubility of water vapor in the uncoated vessel 1002, such as an uncoated PET vessel 1002, is constant and/or predictable. Optionally, resins having sufficient solubility of other atmospheric gases including water vapor, such as, for example, N2, O2, Ne, H2, CO, Ar, CH4, Kr, C2H6, C2H4, Xe, and water vapor, among others, can be considered, individually or collectively, as test gas(es).
The test fixture allows for multiple ways of exposing the vessel 1002 to the test gas(es). For example, according to one process, test gas(es) may be delivered into the inner area 1036 of the cover 1032 through hosing or tubing that is connected to the connector 1040. The test gas(es) may remain in the inner area 1036 at a predetermined pressure, such as, for example, approximately 40 psig to 230 psig (27.58 N/cm2 to 158.58 N/cm2), that facilitates permeation of the test gas(es) through the wall 1005 and into the interior area 1004 of the vessel 1002. However, the pressure of the test gases may also range from 25 psig to 2000 psig (17.24 N/cm2 to 1,378.95 N/cm2), and more specifically 200 psig to 2000 psig (137.89 N/cm2 to 1,378.95 N/cm2). After a predetermined period of time, a vacuum and/or mass extraction unit or mass spectrometer that is operably connected to the passageway 1014 by the vacuum port 1042 may be activated, thereby withdrawing gases from the interior area 1004. The mass extraction unit may then measure the molecular flow of test gas(es) (μg/min) being evacuated from the vessel 1002 in order to determine the quantity of test gas that permeated through the vessel 1002. The mass spectrometer unit may then measure the concentration of test gas(es) being evacuated from the vessel 1002 in order to determine the quantity of test gas that permeated through vessel 1002. Such data may then be compared to known information to determine the integrity of the barrier coating of the vessel 1002, such as, for example, similar data for vessels 1002 having known barrier coating integrity.
Additionally, in addition to or in lieu of test gas being delivered to the inner area 1036 of the cover 1032, permeable test gas(es) may be delivered to the internal area 1004 of the vessel 1002. For example, test gas may be delivered through the passageway 1014 and opening 1003 before entering the interior area 1004 of the vessel 1002. The test gas may be retained in the interior area 1004 at a predetermined pressure and for a predetermined period of time to allow the test gas the opportunity to be absorbed by the material of the vessel 1002, such as the plastic material used to form the wall 1005. Moreover, the test gas(es) may be absorbed by portions of the wall 1005 that have a deficient or defective barrier coating. At least a portion of the test gas that was not absorbed by the vessel 1002 may later be evacuated from the interior area 1004.
According to other embodiments, the vessel 1002 may be preconditioned by exposure to test gas(es) in another structure before being secured to the off gas test fixture 1000. Thus, according to certain embodiments, the exposure of the vessel 1002 to test gas(es) at step 1110 may occur before the vessel 1002 is evacuated at step 1100. For example, after being subjected to a vacuum, the vessel 1002 be subjected to a test gas(es), such as, for example, CO2, for a period of time, such as, for example 15 to 30 minutes at pressures that may facilitate absorption of the test gas(es) by the vessel 1002, such as, at pressures of approximately 40-230 psig (27.58-158.58 N/cm2). During this time, test gas(es) may have the opportunity to be absorbed by the material of the vessel 1002, including, for example, portions of the wall 1005 along the interior surface 1007 that have a deficient or defective barrier coating.
According to certain embodiments, the pressure level of the test gas(es) that the vessel 1002 is exposed to, such as during preconditioning or in the off gas test fixture 1000, may be elevated so as to increase that the quantity of test gas(es) that is/are absorbed, or permeates into, the material of the vessel 1002. Such increases in absorption and/or permeation of test gas(es) into the vessel 1002 may be further elevated when the barrier coating of the vessel 1002 is defective or deficient. This increased absorption may then result in, during subsequent testing of the barrier coating's integrity, an increase in the quantity of the test gas(es) that is/are desorbed or otherwise released from the material of the vessel 1002. Thus, vessels 1002 having deficient or defective barrier coatings may be readily distinguishable from those having acceptable coating integrities due to the elevated levels of detected desorbed test gases. After this preconditioning, the vessel may be removed from the preconditioning structure and secured to the off gas test fixture 1000
At step 1120, with vessel 1002 secured to the off gas test fixture 1000, the gases (either test gas(es) or other gases) are evacuated from the vessel and/or inner area 1036. Then at step 1130, the barrier coating integrity is evaluated. For example, a mass extraction test may be conducted in which test gas(es) that was absorbed by the vessel 1002 is desorbed, and magnitude of molecular flow of the desorbed test gas is measured to provide an indication of quantity of test gas that was absorbed by the material of the vessel 1002. Further, in addition to or in lieu of mass extraction testing, the barrier coating integrity may also be evaluated by quantifying the concentration of particular gases using a mass spectrometer. With both tests, it is expected that the molecular flow will decrease with increases in barrier coating integrity due to the barrier coating causing a reduction in the ability of the test gas to permeate into, or be absorbed by, the molded plastic of the vessel 1002.
Testing using the off gas test fixture 1000 and a mass extraction unit using an above-discussed process has demonstrated effective, accurate, and relatively fast results in detecting the integrity of the barrier coating on vessels 1002. For example, FIG. 5 illustrates testing using a mass extraction unit in the testing of five different vessels 1002. In these tests, each vessel 1002 was known to have a different degree of barrier coating integrity. Specifically, a first vessel 1002 having a known SiOx barrier coating integrity was tested as a positive control, while the four remaining vessels 1002 each had a single blind hole drilled through the SiOx barrier coating. Drill bits having diameters of 0.01 in. (0.254 mm), 0.080 in. (2.03 mm), 12/64 in. (4.76 mm), and 19/64 in. (7.54 mm) were used to drill holes in the respective vessel 1002.
Each vessel 1002 was preconditioned in a separate apparatus prior to being secured to the test fixture 1000. For example, each vessel 1002 was evacuated for approximately 1 minute before being subjected to a test gas of CO2 for approximately 30 minutes at 40 psig (27.58 N/cm2). At the end of the 30 minutes, the test gas(es) was evacuated. Within approximately 45-90 seconds after the completion of the evacuation of the test gas(es) used during preconditioning, the vessel 1002 secured to the off gas test fixture 1000 and the cover 1032 was secured to the base 1001. A vacuum was also applied to evacuate gases present between the face and side seals 1015, 1018, and a relatively short test was conducted to test the sealing quality of the off gas test fixture 1000.
Following this short test, with the vessel 1002 still under vacuum, the vessel 1002 was tested for mass extraction flow rate. During this test, the vacuum applied to the interior area 1004 resulted in the pressure in the interior area 1004 reaching approximately 1 torr. Additionally, during the testing, a vacuum was continued to be applied to the space between the face seal 1015 and side seal 1018. The interior area 1004 was evacuated for approximately 15 minutes so that CO2 test gas that had been absorbed by the vessel 1002 during preconditioning was able to be desorbed and detected by the mass extraction unit. The result of these detections is shown in FIG. 5.
The vertical axis in FIG. 5 indicates the molecular flow (μg/min) of the desorbed test gas while the horizontal axis indicates the diameter of the drill bit used to drill through the SiOx barrier coating. As shown, the vessel 1002 that did not have a hole drilled through the SiOx barrier coating had a detected CO2 flow rate of approximately 0.300 μg/min. Notably, there is a relatively significant difference between the vessel 1002 without the defect created in barrier coating and the vessels 1002 that had a hole drilled through the SiOx barrier coating. Such distinctions demonstrate that the use of the off gas test fixture 1000 with a mass extraction unit provide a readily identifiable, and relatively quick, indication of defects or deficiencies in barrier coating. Moreover such distinction is readily identifiable between the vessel 1002 without the drilled coating defect and the barrier coating of the vessel 1002 that was subjected to the smallest diameter drill bit (0.01 in. (0.254 mm)).
It has also been discovered that the separation between the detected molecular flow of vessels 1002 with generally acceptable barrier coatings and those with small defects increases as the pressure and time that the vessels 1002 are exposed to the test gas(es) during preconditioning increases. For example, FIG. 6 demonstrates flow rates using test methods similar to those shown described above with respect to FIG. 5 with the exception that during preconditioning sets of vessels 1002 were subjected to CO2 test gas(es) at different pressures, namely, 40, 100, and 230 psig (27.58, 68.95, 158.58 N/cm2). As shown, as the pressure of the test gas(es) increase, the resulting level of separation between the associated positive control vessel 1002 (vessel without a hole drilled through the SiOx barrier coating) and the vessels 1002 having the holes drilled through the SiOx barrier coating increases. However, the degree of separation between the vessels 1002 having defects in the barrier coating, is generally relatively small. Further, differences in the severability of the detected flow for the vessels 1002 having defects may, at least in part, be attributed to differences in the depth at which the drill bit drilled into the vessel 1002.

## Claims

1. An off gas test fixture for testing the barrier coating integrity of a vessel having at least one opening, the off gas test fixture comprising:
an interface portion having a surface and a wall, the surface configured to abut against a portion of the vessel adjacent to the opening, the surface further including a face seal configured to provide a first seal about the opening when the vessel is secured to the off gas test fixture, the wall including a recess configured to house a side seal, the side seal configured to provide a second seal between a portion of the wall of the vessel and the interface portion;
a vacuum line in communication with a space separating the first seal and the second seal, the vacuum line configured to be operably connected to a vacuum to evacuate gas from the space when the vessel is secured to the off gas test fixture;
a source of a test gas that is soluble, absorbed, adsorbed or permeable in or on a surface of the molded material of the wall of the vessel; and
a compression nut configured to threadingly engage at least a portion of the wall of the interface portion, the compression nut further configured to provide a compressive force against the side seal to deform the side seal in a manner that prevents gas from passing through the second seal.

2. An off gas test fixture for testing the barrier coating integrity of a vessel having at least one opening, the off gas test fixture comprising:
an interface portion having a surface and a wall, the surface configured to abut against a portion of the vessel adjacent to the opening, the surface further including a face seal configured to provide a first seal about the opening when the vessel is secured to the off gas test fixture, the wall including a recess configured to house a side seal, the side seal configured to provide a second seal between a portion of the wall of the vessel and the interface portion;
a vacuum line in communication with a space separating the first seal and the second seal, the vacuum line configured to be operably connected to a vacuum to evacuate gas from the space when the vessel is secured to the off gas test fixture;
a source of a test gas that is soluble, absorbed, adsorbed or permeable in or on a surface of the molded material of the wall of the vessel; and
a cover that defines an inner area, the inner area configured to encompass the vessel and interface portion when the cover is secured to a base, and wherein the interface portion extends from the base.

3. The off gas test fixture of claim 2, further including a connector that is operably connected to the cover, the connector having a first end and a second end, the first end being configured for connection to a hose, the second end being in communication with the inner area.

4. The off gas test fixture of claim 2, further including a seal positioned between the cover and the base, the seal configured to prevent gas from passing into or out of the inner area when the cover is secured to the base.

5. A method for testing the barrier coating integrity of a vessel having a wall, at least one opening, and a barrier coating, the method comprising:
providing an off gas test fixture comprising a base and a cover, the base including an interface portion having a surface and the cover generally defining an interior area;
securely engaging a portion of the vessel against the surface of the interface portion of the off gas test fixture;
sealing the engagement between the portion of the vessel and the surface of the interface portion to provide a first gas seal;
sealing an area between a portion of the wall of the vessel and the interface portion to provide a second gas seal, the second gas seal positioned to provide a space between the first gas seal and the second gas seal;
securing the cover to the base with the vessel and the interface portion within the interior area; and
exposing the vessel to a test gas, wherein the gas is delivered into an inner area of the cover, the test gas being soluble by the material of the vessel;
evacuating gas out of the space between the first and second gas seal;
applying a vacuum to the vessel to remove any test gas that had been absorbed by, or permeated into, the vessel; and
measuring the test gas removed by the vacuum to determine the integrity of the barrier coating.

6. The method of claim 5, wherein said measuring includes measuring the molecular flow of the test gas desorbed by, and/or permeated through, the vessel.

7. The method of claim 6, wherein said measuring includes measuring the flow of test gas using of a mass extraction unit.

8. The method of claim 7, wherein said measuring includes quantifying the concentration of the test gas using a mass spectrometer.

9. The method of claim 5, wherein said exposing the vessel to a test gas includes exposing the vessel to the test gas before securely engaging the portion of the vessel against an interface portion.

10. The method of claim 5, further including said delivering a test gas through a passageway in the interface portion and to the interior area of the vessel.

11. The method of claim 10, wherein said evacuating a test gas out of the interior area involves evacuating test gas that has been desorbed by the material of the vessel.

12. The method of claim 5, wherein said securely engaging the portion of the vessel against the surface includes tightening a compression member that abuts against a portion of the vessel, the compression member providing a force to secure the vessel between the compression member and the surface.

13. The method of claim 5, wherein said sealing the engagement between the portion of the vessel and the surface of the interface portion includes deforming an 0-ring positioned in a groove in the upper surface to form the first gas seal.

14. The method of claim 5, wherein said sealing the area between a portion of the wall of the vessel and the interface portion includes engaging a compression nut against a side seal to deform the side seal to form the second gas seal, the side seal being an O-ring.

15. The method of claim 5, wherein the vessel is a vial, syringe, or blood.

16. The method of claim 5, wherein said exposing a vessel to a test gas includes exposing the vessel to a test gas pressure of approximately 25 psig to 2000 psig.

17. The method of claim 5, wherein said exposing a vessel to a test gas includes exposing both the interior area and exterior surfaces of the vessel to the test gas.

18. The method of claim 5, wherein the test gas comprises one or more members selected from the group consisting of: carbon dioxide, helium, nitrogen, oxygen, water vapor, neon, hydrogen, carbon monoxide, argon, methane, krypton, ethane, ethylene, and xenon.

19. The method of claim 5, wherein the test gas consists essentially of a member selected from the group consisting of: carbon dioxide, helium, nitrogen, oxygen, water vapor, neon, hydrogen, carbon monoxide, argon, methane, krypton, ethane, ethylene, and xenon.

20. An off gas test fixture for testing the barrier coating integrity of a vessel having at least one opening, the off gas test fixture comprising:
a base;
an interface portion extending from the base and having a surface and a wall, the surface configured to abut against a portion of the vessel adjacent to the opening, the surface further including a face seal configured to provide a first seal about the opening when the vessel is secured to the off gas test fixture, the wall including a recess configured to house a side seal, the side seal configured to provide a second seal between a portion of the wall of the vessel and the interface portion;
a vacuum line in communication with a space separating the first seal and the second seal, the vacuum line configured to be operably connected to a vacuum to evacuate gas from the space when the vessel is secured to the off gas test fixture; and
a cover configured to be secured to the base to define an inner area between them, the inner area configured to encompass the vessel and interface portion when the cover is secured to the base.

21. An off gas test fixture for testing the barrier coating integrity of a vessel having at least one opening, the off gas test fixture comprising:
an interface portion having a surface and a wall, the surface configured to abut against a portion of the vessel adjacent to the opening, the surface further including a face seal configured to provide a first seal about the opening when the vessel is secured to the off gas test fixture, the wall including a recess configured to house a side seal, the side seal configured to provide a second seal between a portion of the wall of the vessel and the interface portion;
a vacuum line in communication with a space separating the first seal and the second seal, the vacuum line configured to be operably connected to a vacuum to evacuate gas from the space when the vessel is secured to the off gas test fixture; and
a compression nut, the compression nut configured to threadingly engage at least a portion of the wall of the interface portion, the compression nut further configured to provide a compressive force against the side seal to deform the side seal in a manner that prevents gas from passing through the second seal.