U.S. patent application number 12/624717 was filed with the patent office on 2010-11-25 for method of packaging and package for sensors.
This patent application is currently assigned to Edwards Lifesciences Corporation. Invention is credited to Gregory J. Carlin, Patrick Carlin, Kenneth Curry, Todd Fjield, Michael J. Higgins.
Application Number | 20100293892 12/624717 |
Document ID | / |
Family ID | 42243287 |
Filed Date | 2010-11-25 |
United States Patent
Application |
20100293892 |
Kind Code |
A1 |
Curry; Kenneth ; et
al. |
November 25, 2010 |
Method of Packaging and Package for Sensors
Abstract
There are provided methods of packaging and packages that
prevent damage of the package contents while maintaining sterility
and that limit the negative effects of sterilization on sensors
such as enzyme sensors. A method of packaging an enzyme sensor
includes providing an enzyme sensor such as a glucose oxidase
sensor in a gas impermeable package comprising one or more of
oxygen and water, removing a significant portion of the oxygen and
water present in the package, and sealing the package. The
resulting package comprises the enzyme sensor in an atmosphere that
is substantially free of oxygen and water. The package can also
include a pressure indicator that indicates when the package has
exceeded a predetermined pressure.
Inventors: |
Curry; Kenneth; (Oceanside,
CA) ; Fjield; Todd; (Laguna Hills, CA) ;
Higgins; Michael J.; (Huntington Beach, CA) ; Carlin;
Patrick; (Dana Point, CA) ; Carlin; Gregory J.;
(Irvine, CA) |
Correspondence
Address: |
EDWARDS LIFESCIENCES CORPORATION
LEGAL DEPARTMENT, ONE EDWARDS WAY
IRVINE
CA
92614
US
|
Assignee: |
Edwards Lifesciences
Corporation
Irvine
CA
|
Family ID: |
42243287 |
Appl. No.: |
12/624717 |
Filed: |
November 24, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61122246 |
Dec 12, 2008 |
|
|
|
Current U.S.
Class: |
53/403 ;
206/305 |
Current CPC
Class: |
B65D 81/2084 20130101;
A61B 5/14865 20130101; A61B 5/14532 20130101; B65D 81/05 20130101;
B65D 81/2061 20130101; A61B 2562/242 20130101 |
Class at
Publication: |
53/403 ;
206/305 |
International
Class: |
B65B 31/00 20060101
B65B031/00; B65D 85/38 20060101 B65D085/38 |
Claims
1. A method of packaging an enzyme sensor, comprising: providing an
enzyme sensor in a gas impermeable package, said package being
inflatable and sealable, and comprising one or more of oxygen and
water; removing a significant portion of the oxygen and water
present in the package by flushing the package with an inert gas;
inflating the package with excess pressure of said inert gas, and
sealing the package, wherein the package is inflated such that the
packaged material including the enzyme sensor cannot touch more
than one non-adjacent surface of the package at a time.
2. The method according to claim 1, wherein said inert gas is
nitrogen.
3. The method according to claim 1, further comprising the step of
exposing the sealed package to radiation.
4. The method according to claim 3, wherein the radiation is e-beam
radiation.
5. The method according to claim 3, wherein the radiation is gamma
radiation.
6. The method according to claim 1, wherein the package is a metal
foil-lined pouch.
7. The method according to claim 1, wherein the enzyme sensor is a
glucose oxidase sensor.
8. The method according to claim 1, wherein the enzyme sensor is
provided on a catheter.
9. The method according to claim 8, wherein the catheter is
provided on a sheet or tray and affixed thereto.
10. The method according to claim 1, wherein the gas impermeable
package is a flexible material.
11. A sensor package, comprising: an enzyme sensor stored in a
sealed gas impermeable package, said package being inflated with an
inert gas such that the packaged material including the enzyme
sensor cannot touch more than one non-adjacent surface of the
package at a time.
12. The package according to claim 11, wherein the package is
substantially free of oxygen and water.
13. The package according to claim 11, wherein the package includes
no more than 1 mm Hg oxygen.
14. The package according to claim 11, wherein the enzyme sensor is
a glucose oxidase sensor.
15. The package according to claim 11, wherein said inert gas is
nitrogen.
16. The package according to claim 11, wherein the package is a
metal foil-lined pouch.
17. The package according to claim 11, wherein the enzyme sensor is
provided on a catheter.
18. The package according to claim 17, wherein the catheter is
provided on a sheet or tray and affixed thereto.
19. The package according to claim 11, wherein the gas impermeable
package is a flexible material.
20. A method of packaging an enzyme sensor, comprising: providing
an enzyme sensor in a gas impermeable package, wherein at least a
portion of the package is a rigid or semi-rigid material and the
package comprises one or more of oxygen and water; removing a
significant portion of the oxygen and water present in the package
by drawing a vacuum on the package; and sealing the package.
21. The method according to claim 20, further comprising the step
of exposing the sealed package to radiation.
22. The method according to claim 21, wherein the radiation is
e-beam radiation.
23. The method according to claim 21, wherein the radiation is
gamma radiation.
24. The method according to claim 21, wherein the package comprises
a tray.
25. The method according to claim 24, wherein the tray is
thermoformed.
26. The method according to claim 25, wherein said sealing step
comprises heat sealing a film layer onto said thermoformed
tray.
27. The method according to claim 21, wherein the enzyme sensor is
a glucose oxidase sensor.
28. The method according to claim 21, wherein the enzyme sensor is
provided on a catheter.
29. A sensor package, comprising: an enzyme sensor stored in a
sealed gas impermeable package, said package being vacuum sealed
and being substantially free of oxygen and water.
30. The package according to claim 29, wherein the package includes
no more than 1 mm Hg oxygen.
31. The package according to claim 29, wherein the enzyme sensor is
a glucose oxidase sensor.
32. The package according to claim 29, wherein at least a portion
of the package is a rigid or semi-rigid material.
33. The package according to claim 32, comprising a thermoformed
tray.
34. The package according to claim 33, further comprising a film
layer heat sealed to said thermoformed tray.
35. The package according to claim 29, wherein the enzyme sensor is
provided on a catheter.
36. A sensor package comprising: a pouch including a sensor; and a
pressure indicator that indicates when a particular pressure is
reached adjacent the pressure indicator.
37. The package according to claim 36, wherein the pouch includes
the pressure indicator.
38. The package according to claim 36, wherein the pressure
indicator includes a burst point that avulses when the pressure
indicator reaches a predetermined pressure.
39. The package according to claim 36, wherein the pressure
indicator includes a color indicator that becomes activated when
the pressure indicator reaches a predetermined pressure.
40. The package according to claim 36, wherein the pressure
indicator provides an audible sound when the pressure indicator
reaches a predetermined pressure.
41. The package according to claim 36, further comprising one or
more isolated chambers wherein the isolated chambers include the
pressure indicator.
42. The package according to claim 41, wherein the pouch also
includes a pressure indicator.
43. The package according to claim 36, wherein the pouch includes
an inner pouch and the inner pouch includes a burst point as a
pressure indicator when the inner pouch reaches a predetermined
pressure.
44. The package according to claim 43, wherein the inner pouch
includes an aqueous electrolytic solution and/or a sterilizing
agent.
Description
CLAIM OF PRIORITY UNDER 35 U.S.C. .sctn.119
[0001] The application claims the benefit of U.S. Provisional
Application No. 61/122,246 filed Dec. 12, 2008, entitled "Method of
Packaging and Package for Sensors" and assigned to the assignee
hereof and hereby incorporated by reference in its entirety.
FIELD AND BACKGROUND
[0002] The present invention relates to methods of packaging and
packages for sensors such as enzyme sensors that prevent damage to
the sensor and that maintain sterility of the sensor.
[0003] Sensors are known in the medical industry for use in
analyzing fluids such as blood. These sensors generally have to be
sterilized for use in the medical environment; however, known
sterilization methods can result in degradation of sensor
performance and a reduction in the sensor's shelf life. In
addition, packaging delicate medical devices such as sensors
requires that particular care be taken such that damage to either
the sensor or the package itself does not occur. In particular,
damage to the sensor can compromise performance of the device and
damage to the package can compromise sterilization of the
sensor.
[0004] One type of sensor used in the medical industry is an enzyme
sensor. Glucose oxidase (GOx)-based enzyme sensors, for example,
are used to measure blood glucose concentration. An enzyme sensor
includes an enzyme that is immobilized using a membrane at the
surface of an electrode. The membrane limits diffusion to the
enzyme layer. Typically, these sensors are sterilized using
radiation. However, radiation has been shown to denature the
enzymes used in the sensor and to modify the polymer structure of
the membranes thereby increasing the permeability of the membranes.
Therefore, the amount of radiation used to sterilize enzyme sensors
is preferably limited. Alternatively, steps must be taken to limit
the effect sterilization has on the enzyme sensors.
[0005] The maintenance of low bioburden levels is necessary during
manufacturing to minimize the radiation dose required to ensure the
sterilization of enzyme sensors. Typically, lower bioburden levels
are accomplished by limiting human contact with the sensor during
production. However, maintaining low bioburden levels has the
negative effect of increasing production time by requiring
additional cleaning steps, increasing production cost by requiring
replacement of gowns, gloves and other equipment used to maintain a
sterile environment, and reduced yield resulting from the rejection
of products not having the desired bioburden levels. This becomes
particularly problematic for more complex devices where the
bioburden levels are generally higher or at least much more
difficult to minimize.
[0006] Furthermore, if the enzyme sensor is exposed to moisture and
oxygen during sterilization, it can further reduce the shelf life
of the enzyme sensor. In particular, the formation of ozone by
subjecting oxygen and water to sterilization can result in
denaturing enzymes. A reduction of ozone formation is typically
accomplished by using lower radiation doses by controlling
bioburden levels thereby limiting the amount of ozone formed by
radiation. However, maintaining low bioburden levels has its own
issues as discussed above.
BRIEF SUMMARY
[0007] There are provided methods of packaging and packages that
prevent damage of the sensors while maintaining sterility and that
limit the negative effects of sterilization on sensors. A method of
packaging a sensor such as an enzyme sensor includes providing an
enzyme sensor such as a glucose oxidase sensor in a gas impermeable
package comprising one or more of oxygen and water, removing a
significant portion of the oxygen and water present in the package,
and sealing the package. The resulting package comprises the enzyme
sensor in an atmosphere that is substantially free of oxygen and
water, e.g., having an oxygen content of no more than 1 mm Hg.
[0008] In some embodiments, a method of packaging an enzyme sensor
includes providing an enzyme sensor in a gas impermeable package,
wherein the package is inflatable and sealable, and comprises one
or more of oxygen and water. The package can be a flexible
material. A significant portion of the oxygen and water present in
the package is removed by flushing the package with an inert gas
such as nitrogen. The package is then inflated with excess pressure
of the inert gas and sealed, such that the packaged material
including the enzyme sensor cannot touch more than one non-adjacent
surface of the package at a time. Typically, the packaged material
includes a catheter onto which the enzyme sensor is situated and
can further include a tray or sheet such as a cardboard sheet onto
which the catheter can be mounted or fixed. The sealed package can
be exposed to radiation such as e-beam or gamma radiation, or other
known means for medical use.
[0009] In some embodiments, a method of packaging an enzyme sensor
includes providing an enzyme sensor in a gas impermeable package,
wherein at least a portion of the package is a rigid or semi-rigid
material and the package comprises one or more of oxygen and water.
A significant portion of the oxygen and water present in the
package can be removed by drawing a vacuum on the package and
sealing the package. For example, the package can be a thermoformed
tray and the method can, include heat sealing a film layer onto the
thermoformed tray to seal the package. The sealed package can be
exposed to radiation such as e-beam or gamma radiation, or other
known means for medical use.
[0010] The removal of a significant amount of the oxygen and water
present in the package results in a sensor package that is
substantially free of oxygen and water. Thus, when radiation such
as e-beam or gamma radiation is used to sterilize the package
contents, it can be used at higher doses than those presently used
for sterilizing enzyme sensors. This is because the removal of
oxygen results in a reduction in the production of free radicals
and thus the production of ozone in the package in the
sterilization process.
[0011] The packaging methods allow enzyme sensors to be produced
more quickly and more cheaply than by prior art methods wherein the
effects of sterilization are mitigated by controlling bioburden
alone. Furthermore, as there are many attributes of sensors that
are difficult to control individually at design time, it is
possible to design a sensor for the best performance without the
need to focus on the effects of sterilization and the methods that
must be used to mitigate the effects of sterilization. In addition,
the packaging methods allow for a simple but reliable way to
package the sensor without increasing mass, which is costly to ship
and which can create mask areas during sterilization. These mask
areas can make sterilization less predictable and can require
higher doses of radiation, thereby possibly further degrading
sensor performance.
[0012] In some embodiments, a sensor package comprises a pouch
including a sensor and a pressure indicator that indicates when a
particular pressure is reached adjacent the pressure indicator. The
pouch can include the pressure indicator and/or the pressure
indicator can be provided elsewhere in the package such as in one
or more isolated chambers. In some embodiments, the pressure
indicator can include a burst point that avulses when the pressure
indicator reaches a predetermined pressure, a color indicator that
becomes activated when the pressure indicator reaches a
predetermined pressure, and/or an audible sound when the pressure
indicator reaches a predetermined pressure. The pouch can, in some
embodiments, include an inner pouch and the inner pouch can include
a burst point as a pressure indicator when the inner pouch reaches
a predetermined pressure. The inner pouch can further include an
aqueous electrolytic solution and/or a sterilizing agent.
[0013] These and other features and advantages will become more
readily apparent to those skilled in the art upon consideration of
the following detailed description and accompanying figures.
BRIEF DESCRIPTION OF THE FIGURES
[0014] FIG. 1A is a side view of a multilumen catheter
assembly.
[0015] FIG. 1B is a magnified detail of the distal end of the
multilumen catheter of FIG. 1A including an enzyme sensor.
[0016] FIG. 2 is a top view of a catheter including an enzyme
sensor and a package prior to insertion of the catheter into the
package.
[0017] FIG. 3 is a side view of a package including a catheter that
includes an enzyme sensor.
[0018] FIG. 4 is a perspective view of the sealed and inflated
package comprising a catheter that includes an enzyme sensor.
[0019] FIG. 5 is a top view of a catheter that includes an enzyme
sensor provided in tray.
[0020] FIG. 6 is a top view of a pouch that includes a pressure
indicator in the form of a burst point.
[0021] FIG. 7 is a top view of a package that includes a pouch and
one or more compartments that include pressure indicators.
[0022] FIG. 8 is a top view of a pouch that includes a inner
compartment that can include a liquid that enters the pouch at a
particular pressure.
DETAILED DESCRIPTION
[0023] As used in the specification, and in the appended claims,
the singular forms "a", "an", "the", include plural referents
unless the context clearly dictates otherwise. The term
"comprising" and variations thereof as used herein is used
synonymously with the term "including" and variations thereof and
are open, non-limiting terms.
[0024] Methods of limiting possible damage to the sensor or the
packaging material during shipping comprise providing an enzyme
sensor such as a glucose oxidase sensor in a gas impermeable
package. The methods can also limit the negative effects of
sterilization on enzyme sensors.
[0025] In the normal process for producing a package and providing
the sensor within the package, the package can include one or more
of oxygen and water. Furthermore, regardless of the process used to
produce the package and the desire to minimize the bioburden,
microorganisms will generally exist in the package. In the
packaging methods, a significant portion of the oxygen and water
present in the package is removed using an inert process, i.e., a
process that does not have an appreciable effect on the
microorganisms present in the package. For example, the inert
process would kill less than 50%, generally less than 25% and
typically less than 10% of the microorganisms present in the
package. The removal of a significant amount of the oxygen and
water present in the package results in a sensor package that is
substantially free of oxygen and water, e.g., having less than 1 mm
Hg of oxygen prior to sterilization.
[0026] In some embodiments, the sensor can be provided on a
catheter. For example, FIG. 1A illustrates a multilumen catheter
assembly 10 in which a sensor 20 is integrated into the catheter.
The catheter assembly 10 can include multiple infusion ports 32a,
32b, and 32c (collectively referred to as reference number 32) and
one or more electrical connectors 34 disposed adjacent to a
proximal end 36 of the catheter assembly 10. One or more lumens
38a, 38b, and 38c (collectively referred to as reference number 38)
can connect each infusion port 32a, 32b, and 32c, respectively, to
a junction 40. Similarly, a conduit 42 can connect an electrical
connector 34 to the junction 40, and can terminate at junction 40,
or at one of the lumens 38a-38c (as shown). Although the particular
embodiment shown in FIG. 1A is a multilumen catheter having three
fluid lumens and one electrical lumen, other embodiments having
other combinations of lumens and connectors can be used, including
a single lumen catheter, a catheter having multiple electrical
connectors, etc. In some embodiments, one of the lumens and the
electrical connector can be reserved for a probe or other sensing
element mounting device, or one of the lumens can be open at its
proximal end and designated for insertion of the probe or biosensor
mounting device.
[0027] The junction 40 connects the lumens 38a-38c and the conduit
42 to a narrow elongated tube 44 that forms an insertion portion of
the catheter assembly 10. The tube 44 is typically cylindrical,
having a circular or somewhat oval cross section defining a
longitudinal axis extending therethrough. The tube 44 can be formed
from any material, including synthetic materials such as silicone,
polyurethane, polyethylene, and the like. Through the junction 40,
each of the lumens 38a-38c extend in separate parallel paths for
some distance into the distal end of tube 44. One or more support
structures 46 within the tube 44 can be disposed along the length
of the catheter to provide rigidity.
[0028] The distal end 48 of the catheter assembly 10 is shown in
greater detail in FIG. 1B. At one or more intermediate locations
along the distal end, the tube 44 can include one or more recesses
formed in an outer wall of the tube. In some embodiments, the
recess can define an opening in the outer wall of the tube through
which a body fluid can flow into a lumen that is in communication
with the opening. In some embodiments, the recess can define a port
formed in the outer wall of the tube that defines an opening
through which a bodily fluid can flow through the port and into the
lumen, and vice versa. In the illustrated embodiment, the ports
include the intermediate ports 50a and 50b, and an end port 50c
(collectively referred to as reference number 50) that can be
formed towards the distal tip of tube 44. Each port 50a-50c can
correspond respectively to one of the lumens 38a-38c or conduit 42.
That is, each lumen can define an independent channel extending
from one of the infusion ports 32a-32c and conduit 42 to one of the
ports 50a-50c located towards the distal end of the tube 44.
[0029] As shown in FIGS. 1A and 1B, the catheter 10 can include the
sensor 20 proximate to the distal end 48 of the catheter for
monitoring one or more analytes. The enzyme sensor can include one
or more electrodes 62, 64, 66 created on a surface of a flexible
substrate and associated with the catheter 10. The sensor 20 can
communicate with the lumen 38 in the catheter 10 such that an
active portion, e.g., a portion containing an electrode, can be
exposed to space outside the tube 44. Electrical wires 68 coupled
to electrodes 64 and 66 can extend from the sensor 20 through the
lumen 38 to provide a conductive path through the lumen 38 and the
conduit 42 that can terminate at the electrical connector 34. The
electrical wires 68 can be attached to the sensor elements with a
weld, solder, conductive adhesive, such as a conductive epoxy, and
the like. In some embodiments, the electrical wires 68 can be
bonded to the sensor 20. Although the electrical wires 68 are drawn
such that they terminate within the tube 44, the electrical wires
will typically extend and communicate with an electrical connector,
e.g., electrical connector 34.
[0030] The sensor provided on a catheter can be mounted or affixed
to an insert tray or sheet 70. For example, in FIG. 2, the sensor
20 is provided on catheter 10 and the catheter 10 is mounted onto
the tray or sheet 70. The tray or sheet 70 can be made of a
suitable material such as a cardboard. The catheter 10 can be
further affixed to the cardboard sheet using plastic clips, plastic
ties or plastic coated metal ties 72. As shown in the side view of
the catheter 10 and the tray or sheet 70 illustrated in FIG. 3,
portions of the catheter 74 and the ties 72 can provide high points
or rough points in the material to be packaged 76.
[0031] As shown in FIG. 3, the material to be packaged 76 can be
inserted into a gas impermeable package 80 that can be sealed and
inflated. For example, a heat-sealable foil pouch made from a
polyester outer layer, a polyethylene inner layer, and an aluminum
lining layer can be used as the package 80. The material to be
packaged 76 can be inserted through an open end 82 of a package 80
including two separate faces 84 and 86, and a closed end 88.
[0032] Once the material to be packaged 76 is placed in the package
80, oxygen and water from the package can be removed by flushing
the package with an inert gas. For example, nitrogen, a noble gas,
or a combination thereof can be used to flush the package contents.
These gases are provided in dry form, with a moisture content of
less than 1%, more preferably less than 0.1%. This can be
accomplished prior to sealing the package by using an opening in
the package (such as open end 82) for entry of the inert gas and
driving out any gases present in the package such as oxygen and
water using the inert gas. The package can then be inflated with
excess pressure of the inert gas and sealed, such that the packaged
material including the enzyme sensor cannot touch more than one
non-adjacent surface of the package at a time, e.g., cannot touch
both interior faces 84 and 86 of a metal foil-lined pouch. The open
end of the package 82 can then be sealed via known means such as
heat sealing resulting in a sealed package such as the package 80
shown in FIG. 4.
[0033] By having the package 80 is at least partially inflated with
an inert gas, the interior components of the package (the packaged
material 76) are protected from damage upon external pressure. In
particular, as pressure is applied, the trapped gases push back on
the pouch increasing resistance. This pressure will match the
external pressure and negate it, thus preventing damage to the
contained sensors. For example, when the inflated packaged is
further packaged (e.g. in a box), the movement from shipping will
not cause adjacent packages in the box to damage each other and
will not cause friction to wear a hole in the package. In addition,
when the packaged material cannot simultaneously touch both
horizontal faces of the pouch, the packaged material will not
puncture the pouch during vibration of transportation, which will
ensure sterility of the sensor until time of use.
[0034] In some embodiments, the sensor can be provided in a rigid
or semi-rigid package that has enough rigidity that it does not
significantly collapse when the vacuum is drawn on the package. For
example, the sensor can be provided in a thermoformed tray. In some
embodiments, the sensor can be provided on a catheter and the
catheter provided in a tray. For example, as shown in FIG. 5, a
sensor 20 can be provided on a catheter 10 in a thermoformed tray
90. The thermoformed tray can include inset portions that prevent
the catheter 10 from extending above the upper surface 92 of the
tray. The thermoformed tray 90 can include protrusions 94 and/or
plastic clips 98 that hold the catheter 10 in place within the
tray.
[0035] The sensor 20 and/or catheter 10 provided in the insert tray
90 can be placed in a vacuum chamber wherein the removal of oxygen
and water can be accomplished by drawing a vacuum on the package.
This can be accomplished by removing any gases from the package
using a vacuum process and then sealing the package. For example, a
film (not shown) can be heat sealed along an outer edge 96 of the
package. The package can also be flushed with an inert gas prior to
drawing a vacuum on the package and sealing the package.
[0036] The interior of the package produced by the above methods
can be substantially free of oxygen and water. The environment in
the package typically has an oxygen content of less than 1 mm Hg.
By using appropriate techniques of vacuum cycling with inert gas,
then sealing in vacua, the partial pressure of oxygen can be a
small fraction of the total pressure in the sealed package, which
can be 1 to 10 mm Hg. Likewise, the partial pressure of water in
the sealed package will be a small fraction of the total pressure
as stated previously. Thus, the amount of oxygen can be less than
0.5 mm Hg or even less than 0.1 mm Hg in the sealed package.
Furthermore, the amount of water can be less than 1 mm Hg, less
than 0.5 mm Hg, or even less than 0.1 mm Hg in the sealed
package.
[0037] The sealed package produced by any of the above methods can
be exposed to radiation or any other known means to sterilize the
contents therein. Preferably, e-beam or gamma radiation is used to
sterilize the package contents although other forms of radiation
can alternatively be used. The radiation can be used at higher
doses and/or the sensor package can be at higher bioburden levels
than those presently used for sterilizing enzyme sensors because of
the reduction in the production of free radicals and thus the
production of ozone in the package resulting from the sterilization
process. In particular, in present systems, the required e-beam
dose is in the order of about 19 kGy and requires a bioburden level
to be below about 19.7 CFU's. Using the method of the present
invention, the bioburden level can be greater than 25 CFU's,
greater than 50 CFU's, greater than 75 CFU's, greater than 100
CFU's, greater than 125 CFU's and even greater than 150 CFU's and
still provide a sufficiently sterilized enzyme sensor.
Alternatively, much higher does of radiation at these bioburden
values can be used in the order of 25 kGy or greater, 30 kGy or
greater, 35 kGy or greater, or even 40 kGy or greater, for e-beam
radiation levels.
[0038] A system for producing a package for a sensor can include
means for inserting a sensor (or packaged material including a
sensor) into the package; means for one of flushing the sensor with
an inert gas or drawing a vacuum on the package; optionally means
for inflating the package, and means for sealing the package. The
system can also include means for forming the package includes
thermoforming or trimming a sheet of plastic, or by other means
known in the art. The sensor is typically inserted into the open
package by a conveyor, by hand or by other means known in the art.
The open sensor package can be flushed with an inert gas by
inserting a nozzle into the open end of the pouch and by closing
the bars on an impulse sealer at such a time as to leave the pouch
partially inflated. The resulting package can be sterilized by
subjecting the package to radiation using e-beam or gamma radiation
or another process known in the art.
[0039] As an alternative to or in addition to including means for
flushing with an inert gas, the package can include means of
drawing a vacuum and sealing the package while it is subjected to
the vacuum and suitable means are known in the art. For example, a
vacuum can be drawn on a rigid package by using a pump to pull air
and other gases from the open package by placing the package in a
vacuum chamber and then sealing said package, or by other means
known in the art. The open package can be sealed using a heat
sealing process or another process known in the art.
[0040] The sensors packaged according to the invention are
particularly useful in systems where enzyme sensors are typically
used. For example, the sensors can be used for real-time
measurement of redox active chemical species in a bodily fluid by
taking in vivo measurements; however, the membranes and electrodes
are also useful otherwise. For example, the sensors can be used for
continuous measurement in a laboratory setting. In certain
embodiments, the sensors can be used with automated testing
equipment.
[0041] The sensor can be provided within a probe or catheter for
intravenous insertion into a patient. When the sensors and methods
of the invention find use for in vivo testing in a live subject,
placement of the sensor can be by any useful method known in the
art using known devices, such as catheters. In these settings, the
sensor can function as an amperometric sensor while immersed in a
patient's bloodstream. In certain embodiments, catheters such as a
multilumen catheter, a central venous catheter (CVC), a pulmonary
artery catheter (PAC), a peripherally inserted central catheter
(PICC), or other commonly used peripheral intravenous (IV) lines
can provide a suitable platform for effective intravenous
positioning of the sensor. For example, the sensor can be
positioned in the patient's bloodstream by inserting a probe
including the sensor through a CVC or PAC or through a peripheral
IV catheter or by using an introducer. One advantage of using a CVC
or PAC for installing an intravenous sensor is its ability to reach
the largest blood vessels of the body where a sensor can be exposed
to an abundant flow of blood. Further, certain embodiments of the
invention can be economically employed for use with multilumen
catheters. Alternately, the sensor can be attached to a venous
arterial blood management protection (VAMP) system by drawing a
blood sample from the intravascular space and exposed to the sensor
ex vivo.
[0042] Specifically, in one embodiment, a sensor according to the
invention can be described as being in association with a catheter.
In such embodiments, "association" comprises any method of
combining a sensor and a catheter allowing for in vivo sensing
using the sensor. For example, association can refer to direct
attachment of the sensor to a surface of the catheter subject to
ambient conditions. Association can also refer to a combination of
the sensor and a catheter such that the sensor is directly adjacent
the catheter (i.e., in a working proximity thereto) but not
attached thereto. Still further, association can encompass
placement of the sensor within a lumen of the catheter. Thus,
association means that the sensor and the catheter are sufficiently
related such that placement of the catheter in vivo likewise
results in placement of the sensor in vivo.
[0043] In embodiments where a pouch or bag is used, the pouch or
bag can include an indicator that shows when the pouch or bag has
exceeded a maximum pressure. For example, as shown in FIG. 6, a
pouch 100 including the sensor (or a catheter including the sensor
104) can have a weakened location or burst point 102 that avulses
when the pressure exceeds a maximum value. The burst point 102 can
be provided by providing a portion of the pouch 100 with a thinner
film layer or by roughening the surface of the pouch at the
location of the burst point without creating a hole in the pouch.
The burst point 102 can have a color indicator 106 (e.g. a bright
red indicator) that is readily apparent on the pouch 100 and that
can further include a warning not to use the sensor. The color
indicator 106 can be provided on the interior side of the film
forming the pouch 100 and can become colored, e.g., upon exposure
to oxygen. The pouch 100 can be inflated to a predetermined
pressure at a predetermined temperature (e.g. at room temperature)
and a predetermined volume (e.g. the fully inflated volume of the
pouch). Based on the ideal gas law (PV=nRT), a maximum pressure
could be determined that would cause the burst point 102 to avulse.
Accordingly, if the pouch 100 were to burst at the burst point 102,
the end user would know that the pouch exceeded the maximum
pressure.
[0044] In some embodiments, the burst point 102 could alternatively
or additionally provide a sound such as a "pop" that would indicate
to a person involved in the delivery or storage of the sensors
provided in the pouches that the pouches need to be moved to a
higher pressure and/or lower temperature environment to preserve
the sterility of the other sensors provided in the pouches.
[0045] In some embodiments as shown in FIG. 7, a package 110 can
include a pouch 112 including the sensor and one or more isolated
chambers (e.g. 114, 116 and 118) on the package of different
sensitivities that burst progressively based on the pressures the
package is subjected to. For example, the isolated chambers 114,
116 and 118 could have burst points that would burst at 90%, 95%
and 100% of what would be the maximum pressure for the pouch 112.
Alternatively, if the pouch 112 also includes a burst point
provided at 100% of the maximum pressure, the isolated chambers
114, 116 and 118 could have burst points at 85%, 90% and 95% of the
maximum pressure. The isolated chambers 114, 116 and 118 can help
to preserve the sterility of the sensor for pressures below a
maximum pressure.
[0046] In some embodiments as shown in FIG. 8, a pouch 120 can
include an inner compartment 122 that includes a burst point that
is set to avulse at a particular pressure. The inner compartment
122 can include a liquid (e.g. an aqueous electrolytic solution)
that can wet the sensor or a sterilizing agent that can provide
sterility to the sensor and extend its life. In the event a liquid
is used pre-wet the sensor, the liquid can be used to reduce run-in
time for the sensor.
[0047] The method of the present invention allows enzyme sensors to
be produced more quickly and more cheaply than by prior art methods
wherein the effects of sterilization are mitigated by controlling
bioburden alone. Furthermore, as there are many attributes of
sensors that are difficult to control individually at design time,
it is possible to design a sensor for the best performance without
the need to focus on the effects of sterilization and the methods
that must be used to mitigate the effects of sterilization.
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