Note: Descriptions are shown in the official language in which they were submitted.
CA 02568226 2006-11-30
TITLE
Glucose Sensor Package System.
FIELD OF THE INVENTION
This invention relates to glucose monitor systems and, in particular
embodiments, to glucose sensors for use with glucose monitor systems and to
the
packaging for the glucose sensors. The invention also relates to the size,
shape
and positioning of electrodes on a glucose sensor.
BACKGROUND OF THE INVENTION
Over the years, bodily characteristics have been determined by obtaining
a sample of bodily fluid. For example, diabetics often test for blood glucose
levels. Traditional blood glucose determinations have utilized a painful
finger
prick using a lancet to withdraw a small blood sample. This results in
discomfort
from the lancet as it contacts nerves in the subcutaneous tissue. The pain of
lancing and the cumulative discomfort from multiple needle pricks is a strong
reason why patients fail to comply with a medical testing regimen used to
determine a change in characteristic over a period of time. Although non-
invasive systems have been proposed, or are in development, none to date have
been commercialized that are effective and provide accurate results. In
addition,
all of these systems are designed to provide data at discrete points and do
not
provide continuous data to show the variations in the characteristic between
testing times.
A variety of implantable electrochemical sensors have been developed for
detecting and/or quantifying specific agents or compositions in a patient's
blood.
For instance, glucose sensors are being developed for use in obtaining an
indication of blood glucose levels in a diabetic patient. Such readings are
useful
in monitoring and/or adjusting a treatment regimen which typically includes
the
regular administration of insulin to the patient. Thus, blood glucose readings
improve medical therapies with semi-automated medication infusion pumps of
the external type, as generally described in U.S. Patent Nos. 4,562,751;
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4,678,408; and 4,685,903; or automated implantable medication infusion pumps,
as generally described in U.S. Patent No. 4,573,994. Typical thin film sensors
are described in commonly assigned U.S. Patent Nos. 5,390,671; 5,391,250;
5,482,473; and 5,586,553. See also U.S. Patent No. 5,299,571.
Many of these glucose sensors utilize complex chemical structures and/or
reactions that can degrade over time, if maintained under improper conditions.
Since sensors may be stored for long periods of time after manufacture and
prior
to use, the sensors must be monitored frequently and maintained in areas with
a
carefully controlled environment. The monitoring of sensors is particularly
difficult once the sensors have been sterilized and placed in packages. Often
the
only way to monitor the sensors is to pull a sample and remove it from a
package.
However, this destroys the sterility and results in waste. Also, monitoring
sensors that have been shipped to a user are problematic or difficult.
SUMMARY OF THE DISCLOSURE
It is an object of an embodiment of the present invention to provide an
improved glucose sensor package system, which obviates for practical purposes,
the above mentioned limitations.
Embodiments of the present invention are directed to a glucose sensor
package system that includes a glucose sensor and a protective package that
indicates proper exposure to sterilization or exposure to temperature changes
to
indicate proper temperature control. Also covered are methods of transporting
and sterilizing the package. In addition, further embodiments of the glucose
sensors are directed to the sizing and positioning of the electrodes on the
glucose
sensor.
According to an embodiment of the invention, a glucose sensor package
system for storing and transporting a glucose sensor includes at least one
glucose
sensor, a protective package and at least one temperature exposure indicator.
The
protective package has an interior to hold the at least one glucose sensor in
the
interior of the protective package. The at least one temperature exposure
indicator is used to determine if the protective package has been exposed to
at
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least one exposure temperature relative to a predetermined threshold
temperature
value. In particular embodiments, the at least one exposure temperature is
above
the predetermined threshold temperature, and the at least one temperature
exposure indicator indicates when there has been exposure to the at least one
exposure temperature. For instance, the predetermined threshold temperature is
75° F and the at least one exposure temperature exceeds 75° F,
or the
predetermined threshold temperature is 100° F and the at least one
exposure
temperature exceeds 100° F. In other embodiments, the at least one
exposure
temperature is below the predetermined threshold temperature, and the at least
one temperature exposure indicator indicates when there has been exposure to
the
at least one exposure temperature. For instance, the predetermined threshold
temperature is 36° F and the at least one exposure temperature is below
36° F.
In additional embodiments, the at least one temperature exposure
indicator indicates when the at least one exposure temperature relative to the
predetermined threshold temperature existed for a predetermined period of
time.
For instance, the predetermined period of time can be at least 10 minutes, or
at
least 60 minutes. In other embodiments, the period of time is established as a
function of a magnitude of a difference between the at least one exposure
temperature and the predetermined threshold temperature.
In particular embodiments, the at least one temperature exposure indicator
is attached to the protective package. For instance, the at least one
temperature
exposure indicator may be attached to the interior of the protective package
or an
exterior of the protective package. In further embodiments, the at least one
temperature exposure indicator is contained within the protective package, or
attached to the glucose sensor. In preferred embodiments, the at least one
temperature exposure indicator is a sticker. Other embodiments are directed to
a
method of transporting the glucose sensor in a package system.
According to another embodiment of the invention, a glucose sensor
package system for storing and transporting a glucose sensor includes at least
one
glucose sensor, a protective package, and at least one temperature exposure
indicator. The protective package has an interior within which the at least
one
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glucose sensor is disposed, and an exterior. The at least one temperature
exposure indicator has first and second states, of which the first state
indicates
that the protective package has not been exposed to at least one exposure
temperature relative to a predetermined threshold temperature value, and the
second state indicates that the protective package has been exposed to the at
least
one exposure temperature. The at least one temperature exposure indicator, in
particular embodiments, is attached to the interior of the protective package
or
the exterior of the protective package, is contained within the protective
package,
or is attached to the glucose sensor.
In further particular embodiments, the glucose sensor package system
includes a plurality of glucose sensors, each of which is enclosed within a
separate package. The plurality of separately packaged glucose sensors in turn
are disposed within the interior of the protective package. In more specific
embodiments, the glucose sensor package system includes a plurality of the at
least one temperature exposure indicators, each of which is attached to one of
the
separate packages.
In further embodiments, the glucose sensor package system includes a
plurality of the at least one temperature exposure indicators, each of which
provides an indication of exposure to at least one exposure temperature
relative
to a different predetermined threshold temperature value. These embodiments
afford more precise indications of a maximum temperature to which the package
system has been exposed.
Another embodiment of the present invention is directed to a method of
transporting a glucose sensor. The method includes the steps of providing at
least one glucose sensor. Providing a protective package having an interior.
Holding the at least one glucose sensor in the interior of the protective
package.
Using at least one temperature exposure indicator to determine if the
protective
package has been exposed to at least one exposure temperature relative to a
predetermined threshold temperature value.
A further embodiment of the present invention is directed to a method of
transporting a glucose sensor, the method including the steps of providing a
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glucose sensor package system. The package system including at least one
glucose sensor, a protective package having an interior within which the at
least
one glucose sensor is disposed and an exterior, and at least one temperature
exposure indicator having first and second states. Transporting the glucose
sensor package system, and observing the state of the at least one temperature
exposure indicator to determine if the protective package has been exposed to
the
at least one exposure temperature during transport.
Additional embodiments of the method employ a glucose sensor package
system that includes a plurality of the at least one temperature exposure
indicators, each of which provides an indication of exposure to at least one
exposure temperature relative to a different predetermined threshold
temperature
value. In these embodiments, the observing step includes an observation of the
state of each of the at least one temperature exposure indicators to determine
if
the protective package has been exposed to at least one exposure temperature
relative to at least one of the different predetermined threshold values.
Another embodiment of the present invention is directed to a glucose
sensor package system for sterilizing a glucose sensor using electron beam
sterilization, the system including at least one glucose sensor, a protective
package, and at least one radiation exposure indicator. The protective package
has an interior to hold the at least one glucose sensor in the interior of the
protective package. The at least one radiation exposure indicator is used to
determine if the protective package has been exposed to a predetermined
exposure level of electron beam sterilization. For example, preferred
embodiments have the predetermined exposure level above 2.0 Mrad. Other
embodiments have the predetermined exposure level less than or equal to 5.0
Mrad or above 0.5 Mrad. In further embodiments, the at least one radiation
exposure indicator indicates that the predetermined exposure level existed for
a
period of time.
In particular embodiments, the at least one radiation exposure indicator is
attached to the protective package. For example, the at least one radiation
exposure indicator may be attached to the interior of the protective package,
or an
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exterior of the protective package. In other embodiments, the at least one
radiation exposure indicator may be contained within the protective package.
In
further embodiments, the radiation exposure indicator may be attached to the
glucose sensor. Preferably, the at least one radiation exposure indicator is a
sticker. Other embodiments are directed to a method of sterilizing the glucose
sensor.
Still additional embodiments are directed to a glucose sensor including a
substrate, a working electrode including at least one enzyme and being coupled
to
the substrate, a counter electrode coupled to the substrate, and a reference
electrode coupled to the substrate. In preferred embodiments, the counter
electrode is formed larger than the working electrode, and the working
electrode
is formed larger than the reference electrode. In still further embodiments,
the
working electrode is placed between counter electrode and the reference
electrode. In additional embodiments, the glucose sensor also includes at
least
one attached temperature exposure indicator.
Packaged glucose sensors as described above are also provided in
accordance with further embodiments. Further embodiments include at least one
temperature exposure indicator attached to the packaging and/or to the glucose
sensor.
Other features and advantages of the invention will become apparent from
the following detailed description, taken in conjunction with the accompanying
drawings which illustrate, by way of example, various features of embodiments
of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
A detailed description of embodiments of the invention will be made with
reference to the accompanying drawings, wherein like numerals designate
corresponding parts in the several figures.
Fig. 1 is a is a perspective view illustrating a subcutaneous glucose sensor
insertion set and glucose monitor device embodying the novel features of the
invention;
Fig. 2 is an enlarged longitudinal vertical section taken generally on the
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line 2-2 of Fig. 1;
Fig. 3 is an enlarged longitudinal sectional of a slotted insertion needle
used in the insertion set of Figs. 1 and 2;
Fig. 4 is an enlarged transverse section taken generally on the line 4-4 of
S Fig.3;
Fig. 5 is an enlarged transverse section taken generally on the line 5-5 of
Fig. 3;
Fig. 6 is an enlarged fragmented sectional view corresponding generally
with the encircled region 6 of Fig. 2;
Fig. 7 is an enlarged transverse section taken generally on the line 7-7 of
Fig. 2;
Figs. 8a-c are perspective views, partially cut away, of embodiments of
glucose sensor package systems including a protective package, a glucose
sensor
and a temperature exposure indicator, with the temperature exposure indicator
attached to the exterior of the protective package, the interior of the
protective
package, and the glucose sensor, respectively;
Fig. 9 is an exploded view of a glucose sensor package system that
includes a plurality of individually packaged glucose sensors all disposed
within
a protective package, with each of the individually packaged glucose sensors
having an attached temperature exposure indicator; and
Fig. 10 is a perspective view of a glucose sensor package system
including a plurality of temperature exposure indicators;
Fig. 11 is a view of a label with multiple temperature exposure indicators
in accordance with an embodiment of the present invention;
Fig. 12 is a view of a portion of an "instructions for use" in accordance
with an embodiment of the present invention;
Fig. 13 is a top plan view of a sensor in accordance with an embodiment
of the present invention;
Fig. 14 is a top plan view of the sensor conductors shown in Fig. 13; and
Fig. 15 is an enlarged, partial top plan view of the electrodes of the sensor
shown in Fig. 13.
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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As shown in the drawings for purposes of illustration, the invention is
embodied in a glucose monitor system that is coupled to a subcutaneous glucose
sensor set to provide continuous data recording of the sensor readings for a
period of time. In preferred embodiments of the present invention, the glucose
sensor and glucose monitor are for determining glucose levels in the blood
and/or
bodily fluids of the user. However, it will be recognized that further
embodiments of the invention may be used to determine the levels of other
analytes or agents, characteristics or compositions, such as hormones,
cholesterol, medications concentrations, viral loads (e.g., HIV), or the like.
In
other embodiments, the glucose monitor may also include the capability to be
programmed to take data at specified time intervals or calibrated using an
initial
data input received from an external device. The glucose monitor and glucose
sensor are primarily adapted for use in subcutaneous human tissue. However,
still further embodiments may be placed in other types tissue, such as muscle,
lymph, organ tissue, veins, arteries or the like, and used in animal tissue.
Embodiments may record sensor readings on an intermittent, near continuous or
continuous basis.
Due to the use of enzyme materials, or other complex chemistries, on the
electrodes of the glucose sensor, it is important to maintain the glucose
sensor at
lower temperatures for storage and transport prior to use. Preferably, the
glucose
sensor is stored in a controlled temperature range of 2 to 24° C (or 36
to 75° F) to
provide a minimum long term storage time of 6 months to 2 years. However,
shorter storage times of 1 month or longer storage times of 5 years (or more)
may
be used. In addition, glucose sensors are preferably designed to withstand 1
hour
of 45° C (or 113° F) without substantial de-nature of the
glucose sensor enzyme
or chemistries.
The best approach to assure proper temperature control is to refrigerate
the glucose sensors, but not freeze them. Preferably, the glucose sensors
should
be shipped in temperature controlled vehicles or in individual packages that
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provide temperature control during transportation, such as with a cold pack,
sufficient insulation to maintain temperature after removal from refrigerated
storage, or the like. It is anticipated that transportation may take anywhere
from
a few hours to three days for the glucose sensors to arrive at their intended
destination, and the temperature must be maintained below a predetermined
temperature threshold during this period. In alternative embodiments, other
possibly temperature sensitive materials used in the glucose sensor may also
drive the selection of a temperature range or level.
To satisfy this temperature control need, embodiments of the glucose
sensor and package are augmented with at least one temperature exposure
indicator, such as a temperature sensitive sticker, to indicate if the glucose
sensor
has been exposed to excessive temperatures or has been at elevated
temperatures
for a predetermined period of time. The indicator, such as a dot, plate,
sticker,
packet, or the like, comprises a temperature-sensitive material that turns
color
upon exposure to elevated temperatures. Such temperature-sensitive materials
are well known to those skilled in the art and are readily available
commercially.
Typically, temperature exposure indicators can be obtained from Wahl
Instruments, Inc. of Culver City CA (Part No. 442-100F), United
Desiccants/Humidial of Colton, CA (Part No. HD 11 LC43), or the like.
In preferred embodiments, the temperature exposure indicator turns from
a white (or slight gray) to a dark gray or black after exposure to elevated
temperatures. However, in alternative embodiments, other color combinations
may be used. If the color change does not match the correct temperature
control
color, the user knows from an "instructions for use" (see Fig. 12), which
preferably are supplied with the glucose sensor, not to use the glucose
sensor.
Preferably, the temperature exposure indicator (320, 430, 530, 600, 602) is on
the
exterior of the packaging to minimize any potential for contamination or
reaction
with the temperature indicator materials with the glucose sensor (see Figs. 8b
and
9-11). However, in alternative embodiments, the temperature exposure indicator
320 can be placed on the interior of the package (see Fig. 8a) if formed out
of
materials that will not interact with the glucose sensor, or if the
temperature
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exposure indicator is contained in a sealed package that will prevent
interaction
with the glucose sensor. In further embodiments, multiple temperature exposure
indicators on the packaging can be used (see Figs. 10 and 11 ). Still further
embodiments utilize temperature exposure indicators 600 that indicate
exposures
to a range of temperatures, such as a plurality of discrete temperature
exposure
indicators that are sensitive to particular temperatures (see Fig. 11 ).
According to further embodiments, the temperature exposure indicator
indicates when the glucose sensor has been exposed to an exposure temperature
exceeding a predetermined temperature, for example a temperature exceeding
100° F (or 38° C), for a predetermined period of time or longer,
for example
longer than 60 minutes, to indicate that possible degradation of the glucose
materials may have occurred due to elevated temperature exposure. Alternative
embodiments can indicate a change after exposure to elevated temperatures with
respect to the predetermined temperature for different time periods, for
example
as little as a few seconds if very sensitive materials are used or a specific
threshold must not be exceeded, or as long as 6 hours if generally temperature
insensitive materials or better temperature-stabilized materials are used with
the
selection being dependent on the temperature tolerance of the glucose sensor.
In addition, other embodiments can include temperature exposure
indicators that are sensitive to lower elevated temperatures, such as
80° F (or 27°
C), 75° F (or 24° C), or the Like, which is closely associated
with the preferred
maximum long term storage temperature. If lower temperatures are used, the
exposure time required to cause a change in the temperature exposure indicator
can be lengthened if desired. It is also noted that the temperature exposure
indicators may respond (by the color change) at more rapid rates for higher
temperatures. For instance, a few minutes' exposure to 200° F (or 93
° C) heat
may cause a temperature exposure indicator (that normally takes 1 hour to
change at 100° F (or 38° C)) to change and indicate degradation
in the glucose
sensor. Proper temperature control assures the user that the glucose sensors
will
operate properly and have not suffered degradation to the enzyme, or other
temperature sensitive materials, that could effect the safe use of the device.
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Thus, in particular embodiments, the temperature exposure indicator can
provide an indication of exposure to exposure temperatures relative to the
predetermined temperature that occur for time periods that vary with the
difference between the exposure temperature and the predetermined temperature.
That is, the period of time to is a function F of a magnitude of a difference
D
between the exposure temperature to and the predetermined temperature td.
Depending on the specific temperature-sensitive material used in the
temperature
exposure indicator, the functional relationship can be one of proportionality,
e.g.,
to = k0, with k being a constant that is characteristic of the specific
material; an
exponential relationship, e.g., td = k,exp(kz 4), where k, and k2 are
constants; or
another functional relationship. The particular functional relationship will
depend on the specific temperature-sensitive material employed, and can
readily
be determined by the mutineer without undue experimentation. In other
embodiments, the temperature sensitive material changes immediately upon
exposure to a temperature above a specific threshold, such that it changes in
fractions of a second, seconds or after longer periods.
Figs. 8a-c illustrate embodiments of a glucose sensor package system
according to embodiments of the present invention including a glucose sensor
300, a protective package 310 having an interior 312 and an exterior 314, and
a
temperature exposure indicator 320. In Fig. 8a, glucose sensor 300 is disposed
in
interior 312 of protective package 310, and temperature exposure indicator 320
is
attached to the interior 312 of protective package 310. In Fig. 8b, glucose
sensor
300 is likewise disposed within interior 312, but a temperature exposure
indicator
320 is attached to the exterior 314 of protective package 310. In Fig. 8c, a
temperature exposure indicator 320 is attached directly to glucose sensor 300,
which in turn is disposed within interior 312 of protective package 310.
In Fig. 9, glucose sensor package system 400 includes a plurality of
glucose sensors 410 each packaged in a separate package 412. The packaged
glucose sensors 410 in turn are disposed within the interior 422 of protective
package 420. A separate temperature exposure indicator 430 is affixed to each
package 412. If desired, separate temperature exposure indicators can also be
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affixed to the protective package 420 in a manner similar to that described in
connection with Figs. 8a-b.
In Fig. 10, a glucose sensor package system 500 includes a protective
package 510 having an interior 512 within which glucose sensor 520 is
disposed.
A plurality of temperature exposure indicators 530 are attached to the
protective
package 510. Each of the plurality of temperature exposure indicators 530
preferably provides an indication of exposure to an exposure temperature
relative
to a different predetermined temperature value. For example, a first
temperature
exposure indicator can indicate exposure to an exposure temperature relative
to
80° F (or 27° C), 75° F (or 24° C), or the like, a
second temperature exposure
indicator can indicate exposure to an exposure temperature relative to
100° F, a
third temperature exposure indicator can indicate exposure to an exposure
temperature relative to 120° F (or 49° C), and so on. Further
particular
embodiments also include temperature exposure indicators that provide an
indication that the exposure temperature relative to the predetermined
temperature existed for a predetermined period of time.
Preferred embodiments of the glucose sensor are sterilized by electron
beam sterilization with a preferred single dose of 2.0 Mrads (or 20 kGy).
However, in alternative embodiments, smaller dose levels may be used if
sufficient sterilization may be achieved at the lower dose, such as for
example
0.5 Mrads (5 kGy). Larger doses may also be used, if the glucose sensor
materials are selected and assembled to withstand doses up to 5.0 Mrads (50
kGy). The glucose sensors are preferably sterilized in accordance with
"ANSI/AAMI ST31-190 Guideline for Electron Beam Radiation Sterilization of
Medical Devices, Method Bl" and/or "ISO 11137:1995 Sterilization of Health
Care Products - Validation and Routine Control - Gamma and Electron Beam
Radiation Sterilization, Dose Selection Method 1 ". The sensor materials are
carefully selected with regard to housing materials, cannula materials,
glucose
sensor substrate, electrodes, membranes, enzyme chemistry, lubricants,
insertion
needle materials and the packaging materials, and manufacturing tolerances to
assure the ability to withstand electron beam sterilization and the continued
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proper operation of the glucose sensor after sterilization. In alternative
embodiments, other radiation sterilization methods, such as gamma radiation,
or
the like, or other chemical methods, such as ETO, or the like, may be used.
Preferred embodiments of the glucose sensor with the packaging include
at least one sterilization indicator that indicates when the glucose sensor
and
packaging have been exposed to an electron beam sterilization procedure. The
sterilization indicator, such as a dot, plate, sticker, packet, or the like,
turns color
upon exposure to the electron beam. In preferred embodiments, the
sterilization
indicator turns from a mustard yellow color or orange yellow to a red or
reddish
orange color after sterilization. However, in alternative embodiments, other
color combinations may be used. If the color change does not match the correct
sterilization color, the user knows from an "instructions for use" (see Fig.
12) not
to use the glucose sensor. Preferably, the sterilization indicator is on the
exterior
of the packaging to minimize any potential for contamination or reaction of
the
I S sticker materials with the glucose sensor. However, in alternative
embodiments,
the sterilization indicator may be placed on the interior of the package if
formed
out of materials that will not interact with the glucose sensor or if the
indicator is
contained in a sealed package that will prevent interaction with the glucose
sensor. In further embodiments, multiple indicators, or stickers, on the
packaging may be used. Typical sterilization indicators may be obtained from
NAMSA Products of Kennesaw, GA (Part No. CPI-R03). In addition, the
sterilization indicators can be attached to the packaging and/or glucose
sensors in
a manner similar to that for temperature exposure indicators as shown in Figs.
8a-
11 and described above.
As shown in Figs. 13-15, further embodiments of the glucose sensor 700
are directed towards optimizing the size, shape and orientation of the glucose
sensor electrodes that come in contact with the interstitial fluid during
glucose
sensing. In preferred embodiments, the glucose sensor 700 includes three
electrodes (a working electrode 702, a counter electrode 704 and a reference
electrode 706). To optimize the electrochemistry of the glucose sensing
reaction,
it is preferred that the counter electrode 704 is the largest electrode, the
working
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electrode 702 (i.e., the one with enzymes, or the like) is the next largest
electrode
and the reference electrode 706 is the smallest electrode. Preferably, the
counter
electrode 704 is as large as possible and consistent with sensor insertion
requirements to minimize pain on insertion of the sensor into the body of the
user. For instance, to fit within a 22 gauge needle. However, alternative
embodiments may be sized to fit other gauge needles ranging from 18 gauge to
30 gauge. In addition, making the working electrode a different size effects
the
amount of enzyme that can be placed on the working electrode and affects the
overall life of the glucose sensor. In further preferred embodiments, it has
been
found to optimize the current paths and the electrochemistry to have the
working
electrode 702 located between the counter electrode 704 and the reference
electrode 706. In additional embodiments, it is preferred that the electrode
(i.e.,
conductors) have a line width of 50~ to assure good electrical conduction of a
sensor signal. However, smaller widths down to l Op and anything larger can be
used if a sufficient signal accuracy is provided and the sensor can fit within
a
needle as described above.
Additional specific embodiments of the glucose sensor include a
temperature exposure indicator as described above attached directly to the
sensor.
Turning again to the figures, the above may be used with the glucose
monitor system 1, in accordance with a preferred embodiments of the present
invention that includes a subcutaneous glucose sensor set 10, and a glucose
monitor 100. The subcutaneous glucose sensor set 10 utilizes an electrode-type
sensor, as described in more detail below. However, in alternative
embodiments,
the glucose sensor may use other types of sensors, such as chemical based,
optical based or the like. In further alternative embodiments, the sensors may
be
of a type that is used on the external surface of the skin or placed below the
skin
layer of the user. Preferred embodiments of a surface mounted glucose sensor
would utilize interstitial fluid harvested from the skin.
The glucose monitor 100 generally includes the capability to record and
store data as it is received from the glucose sensor 10, and then includes
either a
data port or wireless transmitter for downloading the data to a data processor
200,
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computer, communication station, or the like for later analysis and review.
The
data processor 200, computer, or the like, utilizes the recorded data from the
glucose monitor to determine the blood glucose history. Preferably, any port
would be water proof (or water resistant) or include a water proof removable
cover. The purpose of the glucose monitor system 1 is to provide for better
data
recording and testing for various patient conditions utilizing continuous or
near
continuous data recording.
The glucose monitor system 1 also removes inconvenience by separating
the complicated monitoring process electronics into two separate devices; a
glucose monitor 100, which attaches to the glucose sensor set 10; and a data
processor 200, computer, communication station, or the like, which contains
the
software and programming instructions to download and evaluate data recorded
by the glucose monitor 100. In addition, the use of multiple components (e.g.,
glucose monitor 100 and data processor 200, computer, communication station,
or the like) facilitates upgrades or replacements, since one module, or the
other,
can be modified or replaced without requiring complete replacement of the
monitor system 1. Further, the use of multiple components can improve the
economics of manufacturing, since some components may require replacement
on a more frequent basis, sizing requirements may be different for each
module,
different assembly environment requirements, and modifications can be made
without affecting the other components.
The glucose monitor 100 takes raw glucose sensor data, such as glucose
data or the like, from the subcutaneous glucose sensor set 10 and assesses it
during real-time and/or stores it for later download to the data processor
200,
computer, communication station, or the like, which in turn analyzes, displays
and logs the received glucose readings. Logged data can be analyzed further
for
detailed data analysis. In further embodiments, the glucose monitor system 1
may be used in a hospital environment or the like. Still further embodiments
of
the present invention may include one or more buttons 122, 124, 126 and 128 on
the glucose monitor 100 to program the monitor 100, to record data and events
for later analysis, correlation, or the like. In addition, the glucose monitor
may
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include an on/off button 130 for compliance with safety standards and
regulations
to temporarily suspend transmissions or recording. The glucose monitor 100
may also be combined with other medical devices to combine other patient data
through a common data network and telemetry system. In alternative
embodiments, the glucose monitor may be designed as a Holter-type system that
includes a Holter-type recorder that interfaces with a glucose monitor,
processor,
computer, or the like.
As shown in Figs. 1-7, a glucose sensor set 10 is provided for
subcutaneous placement of a flexible sensor 12 (see Fig. 2), or the like, at a
selected site in the body of a user. The implantable glucose sensor set 10
includes a hollow, slotted insertion needle 14, and a cannula 16. The needle
14 is
used to facilitate quick and easy subcutaneous placement of the cannula 16 at
the
subcutaneous insertion site. The cannula 16 includes a sensing portion 18 of
the
sensor 12 to expose one or more sensor electrodes 20 to the user's bodily
fluids
through a window 22 formed in the cannula 16. After insertion, the insertion
needle 14 is withdrawn to leave the cannula 16 with the sensing portion 18 and
the sensor electrodes 20 in place at the selected insertion site.
In preferred embodiments, the implantable subcutaneous glucose sensor
set 10 facilitates accurate placement of a flexible thin film electrochemical
sensor
12 of the type used for monitoring specific blood parameters representative of
a
user's condition. Preferably, the sensor 12 monitors blood glucose levels, and
may be used in conjunction with automated or semi-automated medication
infusion pumps of the external or implantable type as described in U.S. Pat.
Nos.
4,562,751; 4,678,408; 4,685,903 or 4,573,994, to deliver insulin to a diabetic
patient. However, other embodiments may monitor other analytes to determine
viral load, HIV activity, bacterial levels, cholesterol levels, medication
levels, or
the like.
Preferred embodiments of the flexible electrochemical sensor 12 are
constructed in accordance with thin film mask techniques to include elongated
thin film conductors embedded or encased between layers of a selected
insulative
material such as polyimide film or sheet. The sensor electrodes 20 at a tip
end of
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the sensing portion 18 are exposed through one of the insulative layers for
direct
contact with patient blood, or other bodily fluids, when the sensor 12 is
subcutaneously placed at an insertion site. The sensing portion 18 is joined
to a
connection portion 24 (see Fig. 2) that terminates in conductive contact pads,
or
the like, which are also exposed through one of the insulative layers. In
alternative embodiments, other types of implantable glucose sensors, such as
chemical based, optical based, or the like, may be used.
As is known in the art, and illustrated schematically in Fig. 2, the
connection portion 24 and the contact pads are generally adapted for a direct
wired electrical connection to a suitable sensor monitor for monitoring a
user's
condition in response to signals derived from the sensor electrodes 20.
Further
description of flexible thin film sensors of this general type are be found in
U.S.
Patent. No. 5,391,250, entitled METHOD OF FABRICATING THIN FILM
SENSORS. The connection portion 24 may be conveniently connected
electrically to the sensor monitor (not shown), a glucose monitor 100, or a
data
processor 200, computer, communication station, or the like, by a connector
block 28 (or the like) as shown and described in U.S. Pat. No. 5,482,473,
entitled
FLEX CIRCUIT CONNECTOR. Thus, in accordance with embodiments of the
present invention, subcutaneous sensor sets 10 are configured or formed to
work
with either a recording, wired or a wireless system.
The sensor 12 is mounted in a mounting base 30 adapted for placement
onto the skin of a user. As shown, the mounting base 30 is a generally
rectangular pad having an underside surface coated with a suitable pressure
sensitive adhesive layer 32, with a peel-off paper strip 34 normally provided
to
cover and protect the adhesive layer 32, until the sensor set 10 is ready for
use.
As shown in Figs. 1 and 2, the mounting base 30 includes upper and lower
layers
36 and 38, with the connection portion 24 of the flexible sensor 12 being
sandwiched between the layers 36 and 38. The connection portion 24 has a
forward section joined to the sensing portion 18 of the sensor 12, which is
folded
angularly to extend downwardly through a bore 40 formed in the lower base
layer
38. In preferred embodiments, the adhesive layer 32 includes an anti-bacterial
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agent to reduce the chance of infection; however, alternative embodiments may
omit the agent. In further alternative embodiments, the mounting base may be
other shapes, such as circular, oval, hour-glass, butterfly or the like.
The insertion needle 14 is adapted for slide-fit reception through a needle
port 42 formed in the upper base layer 36 and further through the lower bore
40
in the lower base layer 38. As shown, the insertion needle 14 has a sharpened
tip
44 and an open slot 46 which extends longitudinally from the tip 44 at the
underside of the needle 14 to a position at Ieast within the bore 40 in the
lower
base layer 36. Above the mounting base 30, the insertion needle 14 may have a
full round cross-sectional shape, and may be closed off at a rear end of the
needle
14. Further description of the needle 14 and the sensor set 10 are found in
U.S.
Patent No. 5,586,553, entitled "TRANSCUTANEOUS SENSOR INSERTION
SET".
The cannula 16 is best shown in Figs. 6 and 7, and includes a first portion
48 having partly-circular cross-section to fit within the insertion needle 14
that
extends downwardly from the mounting base 30. In alternative embodiments, the
first portion 48 may be formed with a solid core; rather than a hollow core.
In
preferred embodiments, the cannula 16 is constructed from a suitable medical
grade plastic or elastomer, such as polytetrafluoroethylene, silicone, or the
like.
The cannula 16 also defines an open lumen 50 in a second portion 52 for
receiving, protecting and guideably supporting the sensing portion 18 of the
sensor 12. The cannula 16 has one end fitted into the bore 40 formed in the
lower layer 38 of the mounting base 30, and the cannula 16 is secured to the
mounting base 30 by a suitable adhesive, ultrasonic welding, snap fit or other
selected attachment method. From the mounting base 30, the cannula 16 extends
angularly downwardly with the first portion 48 nested within the insertion
needle
14, and terminates slightly before the needle tip 44. At least one window 22
is
formed in the lumen 50 near the implanted end 54, in general alignment with
the
sensor electrodes 20, to permit direct electrode exposure to the user's bodily
fluid
when the sensor 12 is subcutaneously placed.
As shown in Figs. 1 and 2, the glucose monitor 100 is coupled to a
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subcutaneous glucose sensor set 10 by a cable 102 through a connector 104 that
is electrically coupled to the connector block 28 of the connector portion 24
of
the subcutaneous glucose sensor set 10. In preferred embodiments, the plug
connector 103 of the cable 102 is connected to the glucose monitor 100 through
a
plug receptacle 105. In alternative embodiments, the cable 102 may be omitted,
and the glucose monitor 100 may include an appropriate connector (not shown)
for direct connection to the connector portion 24 of the subcutaneous glucose
sensor set 10 or the subcutaneous glucose sensor set 10 may be modified to
have
the connector portion 24 positioned at a different location, such as for
example,
the top of the subcutaneous sensor set 10 to facilitate placement of the
telemetered characteristic monitor transmitter over the subcutaneous sensor
set
10. This would minimize the amount of skin surface covered or contacted by
medical devices, and tend to minimize potential electrical interference
induced
by movement of the subcutaneous glucose sensor set 10 relative to the
telemetered characteristic monitor transmitter 100. In further alternative
embodiments, the cable 102 and the connector 104 may be formed as add-on
adapters to fit different types of connectors on different types or kinds of
sensor
sets. The use of adapters would facilitate adaptation of the glucose monitor
100
to work with a wide variety of sensor systems.
The glucose monitor 100 includes a housing I06 that supports a printed
circuit board 108, batteries 110, memory storage 112, the cable 102 with the
plug
connector 103, and the plug receptacle 105 . In preferred embodiments, the
housing 106 is formed from an upper case 114 and a lower case 116 that are
sealed with an ultrasonic weld to form a waterproof (or resistant) seal to
permit
cleaning by immersion (or swabbing) with water, cleaners, alcohol or the like.
In
preferred embodiments, the upper and lower case 114 and 116 are formed from a
medical grade plastic. However, in alternative embodiments, the upper case I
14
and lower case 116 may be connected together by other methods, such as snap
fits, sealing rings, RTV (silicone sealant) and bonded together, or the like,
or
formed from other materials, such as metal, composites, ceramics, or the like.
In
preferred embodiments, the housing 106 is generally rectangular. However, in
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alternative embodiments, other shapes, such as hour glass, disk, oval shaped,
or
the like, may be used. Preferred embodiments of the housing 106 are sized in
the
range of 3.0 square inches by 0.5 inches thick. However, larger or smaller
sizes,
such as 0.5 square inches and 0.15 inches thick or less, and 5.0 square inches
and
1.0 inches thick or more, may be used.
As shown, the lower case 116 may have an underside surface that
includes a belt clip 118 (or the like) to attach to a user's clothing. In
other
embodiments, the underside surface is coated with a suitable pressure
sensitive
adhesive layer, with a peel-off paper strip normally provided to cover and
protect
the adhesive layer, until the glucose monitor 100 is ready for use. In
preferred
embodiments, the adhesive layer includes an anti-bacterial agent to reduce the
chance of infection; however, alternative embodiments may omit the agent. In
further alternative embodiments, the glucose monitor 100 is secured to the
body
by other methods, such as an adhesive overdressing, straps, belts, clips or
the
like.
In preferred embodiments, the cable 102 should also include a flexible
strain relief portion (not shown) to minimize strain on the subcutaneous
sensor
set 10 and prevent movement of the implanted sensor 12, which can lead to
discomfort or dislodging of the glucose sensor set 10. The flexible strain
relief
portion is intended to minimize sensor artifacts generated by user movements
that causes the subcutaneous glucose sensor set IO to move relative to the
glucose
monitor 100.
The interface via the plug receptacle 105 of the glucose monitor 100
connects with the cable plug 103 of the cable 102 that is connected with the
subcutaneous sensor set 10 via the connector 104. In preferred embodiments,
the
sensor interface may be configured in the form of a jack to accept different
types
of cables that provide adaptability of the glucose monitor 100 to work with
different types of subcutaneous glucose sensors and/or glucose sensors placed
in
different locations of the user's body. However, in alternative embodiments,
the
sensor interface is permanently connected to the cable 102. In preferred
embodiments, the printed circuit board 108, and associated electronics, are
CA 02568226 2006-11-30
capable of operating in a temperature range of 0° C and 50° C.
However, larger
or smaller temperature ranges may be used.
Preferably, the battery assembly will use a weld tab design to connect
power to the system. For example, it can use three series silver oxide 357
battery
cells 110, or the like. However, it is understood that different battery
chemistries
may be used, such as lithium, alkaline or the like, and different numbers of
batteries can be used. In further embodiments, the sensor interface will
include
circuitry and/or a mechanism for detecting connection to the subcutaneous
glucose sensor set 10. This would provide the capability to save power and to
more quickly and efficiently start initialization of the subcutaneous glucose
sensor set 10. In preferred embodiments, the batteries 110 have a life in the
range of 3 months to 2 years, and provide a low battery warning alarm.
Alternative embodiments, may provide longer or shorter battery lifetimes, or
include a power port or solar cells to permit recharging of the batteries 110
in the
glucose monitor 100.
In preferred embodiments, the glucose monitor 100 provides power,
through plug receptacle 105 to the cable plug 103 of the cable 102 and then
through the cable connector 104 to the glucose sensor set 10. The power is
used
to drive the glucose sensor set 10. The power connection is also used to speed
the initialization of the sensor 12, when it is first placed under the skin.
The use
of an initialization process can reduce the time for sensor 12 stabilization
from
several hours to an hour or less. The preferred initialization procedure uses
a two
step process. First, a high voltage (preferably between 1.0-1.2 volts -
although
other voltages may be used) is applied to the sensor 12 for 1 to 2 minutes
(although different time periods may be used) to allow the sensor 12 to
stabilize.
Then, a lower voltage (preferably between 0.5-0.6 volts - although other
voltages
may be used) is applied for the remainder of the initialization process
(typically
58 minutes or less). Other stabilization/initialization procedures using
differing
currents, currents and voltages, different numbers of steps, or the like, may
be
used. Other embodiments may omit the initialization/stabilization process, if
not
required by the glucose sensor or if timing is not a factor.
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At the completion of the stabilizing process, an initial reading may be
downloaded from the glucose sensor set 10 and the glucose monitor 100 to the
data processor 200, computer, communication station, or the like, to verify
proper operation of the glucose sensor 10 and the glucose monitor 100. In
alternative embodiments, a fluid containing a known value of glucose may be
injected into the site around the glucose sensor set 10, and then the reading
sent
to the glucose monitor 100 records the data for the known value to provide a
reference point to the recorded data, such as disclosed in U.S. Patent No.
5,951,521, entitled "A SUBCUTANEOUS IMPLANTABLE SENSOR SET
HAVING THE CAPABILITY TO REMOVE OR DELIVER FLUIDS TO AN
INSERTION SITE". During the stabilization process, the glucose monitor 100
checks to determine if the glucose sensor set 10 is still connected. If the
glucose
sensor set 10 is no longer connected, the glucose monitor 100 will abort the
stabilization process and sound an alarm (or flash a light, or download a
signal to
the data processor 200, computer, communication station, or the like, to sound
an
alarm).
In further alternative embodiments, the glucose monitor 100 can be
combined with a glucose sensor set 10 as a single unit. This would be
particularly well adapted where batteries and the glucose monitor 100 can be
made cheaply enough to facilitate changing the glucose monitor 100 with each
new glucose sensor set 10, such as in a Hotter-type monitor, or the like.
As shown in Fig. 2, the data processor 200, computer, communication
station, or the like, may include a display 214 that is used to display the
results of
the measurement received from the sensor 18 in the glucose sensor set 10
received via a download from the glucose monitor 100. The results and
information displayed includes, but is not limited to, trending information of
the
characteristic (e.g., rate of change of glucose), graphs of historical data,
average
characteristic levels (e.g., glucose), or the like. Alternative embodiments
include
the ability to scroll through the data. The display 214 may also be used with
buttons (not shown) on the data processor 200, computer, communication
station,
or the like, characteristic monitor to program or update data in the data
processor
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200. In preferred embodiments, the glucose monitor 100 includes a display 132
to assist the user in programming the glucose monitor 100, entering data,
stabilizing, calibrating, downloading data, or the like.
In further embodiments of the present invention, the data processor 200,
computer, communication station, or the like, may be replaced by a different
device. For example, in one embodiment, the glucose monitor 100
communicates with an RF programmer (not shown) that is also used to program
and obtain data from an infusion pump or the like. The RF programmer may also
be used to update and program the glucose monitor 100, if the glucose monitor
100 includes a receiver for remote programming, calibration or data receipt.
The
RF programmer can be used to store data obtained from the sensor 18 and then
provide it to either an infusion pump, characteristic monitor, computer or the
like
for analysis. In further embodiments, the glucose monitor 100 may transmit the
data to a medication delivery device, such as an infusion pump or the like, as
part
of a closed loop system. This would allow the medication delivery device to
compare sensor results with medication delivery data and either sound alarms
when appropriate or suggest corrections to the medication delivery regimen. In
preferred embodiments, the glucose monitor 100 would include a transmitter to
receive updates or requests for additional sensor data.
Additional embodiments of the present invention may include a vibrator
alarm (or optical indicator such as an L.E.D.) in the either, or both, the
glucose
monitor 100 to provide a tactile (vibration) alarm to the user, so as to
indicate a
glucose sensor set malfunction, improper connection, low battery, missed
message, bad data, interference, or the like. The use of a vibration alarm
provides additional reminders to an audio alarm, which could be important with
someone suffering an acute reaction, or to have non-audio alarms to preserve
and
conceal the presence of the glucose monitor.
While the description above refers to particular embodiments of the
present invention, it will be understood that many modifications may be made
without departing from the spirit thereof. The accompanying claims are
intended
to cover such modifications as would fall within the true scope and spirit of
the
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present invention.
The presently disclosed embodiments are therefore to be considered in all
respects as illustrative and not restrictive, the scope of the invention being
indicated by the appended claims, rather than the foregoing description, and
all
changes which come within the meaning and range of equivalency of the claims
are therefore intended to be embraced therein.
24
