U.S. patent application number 17/511709 was filed with the patent office on 2022-02-17 for continuous glucose monitoring system and method.
The applicant listed for this patent is SANVITA MEDICAL CORPORATION. Invention is credited to Anthony Florindi, Thomas H. Peterson, Handani Winarta.
Application Number | 20220047191 17/511709 |
Document ID | / |
Family ID | 1000005929244 |
Filed Date | 2022-02-17 |
United States Patent
Application |
20220047191 |
Kind Code |
A1 |
Peterson; Thomas H. ; et
al. |
February 17, 2022 |
Continuous Glucose Monitoring System and Method
Abstract
A continuous glucose monitoring system and method has an
inserter assembly for inserting a sensor through the skin and into
subcutaneous tissue where an inserter housing with the sensor
remains on the skin after insertion, a sensor housing cover
attachable to the sensor housing after insertion where the sensor
housing cover has an electronic module and a battery, and an
electronic device equipped with wireless communication for
communicating with the electronic module of the sensor housing
cover assembly, the electronic device configured for receiving
input signals from the sensor, converting the input signals to
analyte date, displaying the analyte data on a user interface of
the electronic device, storing the data for recall, and creating
and/or sending reports of the data.
Inventors: |
Peterson; Thomas H.;
(Wilmington, MA) ; Winarta; Handani; (Nashua,
NH) ; Florindi; Anthony; (Norfolk, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SANVITA MEDICAL CORPORATION |
Waltham |
MA |
US |
|
|
Family ID: |
1000005929244 |
Appl. No.: |
17/511709 |
Filed: |
October 27, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16468047 |
Jun 10, 2019 |
11197627 |
|
|
PCT/US2016/068196 |
Dec 22, 2016 |
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17511709 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/14865 20130101;
A61B 5/14532 20130101; A61B 5/742 20130101; A61B 5/1473
20130101 |
International
Class: |
A61B 5/145 20060101
A61B005/145; A61B 5/1473 20060101 A61B005/1473; A61B 5/1486
20060101 A61B005/1486 |
Claims
1. A method of inserting a sensor subcutaneously, the method
comprising: providing an inserter assembly containing a sensor and
an insertion needle adapted for implanting the sensor into
subcutaneous tissue wherein the inserter assembly requires a
user-perpetrated initial applied force of greater than 1.5 lbs.
that is followed by a decrease in applied force to an applied force
of less than 1.5 lbs; placing the inserter assembly against a
patient's skin; actuating the inserter assembly to thereby implant
the sensor subcutaneously and disengaging a sensor housing
containing the implanted sensor from the inserter assembly; and
removing the inserter assembly from the patient's skin.
2. The method of claim 1 wherein the providing step includes
providing an inserter assembly that requires a user-perpetrated
initial applied force in the range of 1.5 to 2.5 lbs. followed by a
decrease in the applied force for insertion of the needle into the
subcutaneous tissue wherein the applied force of the insertion
needle is in the range of about 0.5 lbs to about 1.3 lbs.
3. The method of claim 1 wherein the providing step includes
providing an inserter assembly that is capable of implanting the
sensor subcutaneously and disengaging the post-actuation inserter
assembly in a time period selected from the group consisting of
less than 0.5 seconds, a range of less than 0.25 seconds to 0.8
seconds, a range of less than 0.5 seconds to 0.8 seconds, a range
of 0.5 seconds to 0.8 seconds, a range of 0.25 seconds to 0.5
seconds, and 0.5 seconds.
4. The method of claim 1 wherein the actuating step implants the
sensor subcutaneously and disengages the post-actuation inserter
assembly in a time period selected from the group consisting of
less than 0.5 seconds, a range of less than 0.25 seconds to 0.8
seconds, a range of less than 0.5 seconds to 0.8 seconds, a range
of 0.5 seconds to 0.8 seconds, a range of 0.25 seconds to 0.5
seconds, and 0.5 seconds.
Description
RELATED APPLICATIONS
[0001] This application is a Divisional Application of U.S.
application Ser. No. 16/468,047, filed Jun. 10, 2019, which is a
National Phase filing of PCT/US2016/068196, filed Dec. 22, 2016.
Each of these patent applications is herein incorporated by
reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0002] The present invention relates generally to continuous
glucose monitoring. More particularly, the present invention
relates to a glucose monitoring system having a subcutaneous
insertable glucose sensor, an inserter assembly and reader.
2. Description of the Prior Art
[0003] Lancets are well-known devices commonly used in the medical
field to make small punctures in a patient's skin to obtain samples
of blood. They are utilized in hospitals, other medical facilities,
and by private individuals such as diabetics for testing droplets
of blood for various analytes. Typically, lancets are used only
once to reduce the risk of HIV, hepatitis and other blood-borne
diseases. The lancet or sharp of these devices is driven into the
patient's skin by a small spring that is cocked by a technician or
user prior to use. The lancet is covered with a protective, safety
cap that keeps the end of the lancet sterile and is removed before
use.
[0004] A variety of lancet devices are available for use by
patients and/or healthcare practitioners. One lancet device is
configured for multiple and/or repeated uses. In this variety, the
user typically pushes a button or other device on a lancet injector
to cause a lancet to penetrate the skin of a patient. More
commonly, the lancet device effectively encases and fires the
lancet into the patient's skin in order to puncture in an accurate,
standardized and consistent manner. The lancet injector may also be
provided with an adaptor cap to control and adjust the depth of
penetration of the needle of the lancet.
[0005] Integrated lancet and sensor devices have been developed
that combine the lancet and test strip or sensor into a single
package. These integrated devices are typically used with a lancet
injector where the integrated lancet and test strip is removed from
the lancet injector and connected to a meter after acquisition by
the test strip of the blood sample produced by the lancet, or used
with a meter with built-in lancet injector.
[0006] More recently, continuous glucose monitoring devices have
been developed for implanting into a patient's skin. Continuous
monitoring systems typically use a tiny implantable sensor that is
inserted under the skin, or into the subcutaneous fat layer to
check analyte levels in the tissue fluid. A transmitter sends
information about the analyte levels by way of, for example, a wire
to a monitor or wirelessly by radio waves from the sensor to a
wireless monitor. These devices are typically implanted for three
to seven days of use to monitor in real-time a patient's glucose
level.
[0007] One such device is disclosed in U.S. Pat. No. 5,299,571 to
John Mastrototaro. The device is an apparatus for implantation of
in-vivo sensors. The apparatus includes a housing, a dual-lumen
tube extending therefrom, and an in-vivo sensor received within one
of the lumens of the tube. A needle is received within the other
lumen of the tube, and is used to insert the tube through the skin.
After implantation, the needle is removed, and the flexible tube
and sensor remain beneath the skin.
[0008] U.S. Patent Application Publication 2010/0022863 (2010,
Mogensen et al.) discloses an inserter for a transcutaneous sensor.
The inserter includes a needle unit and a sensor housing. The
needle unit includes a needle hub and a carrier body. The sensor
housing and the needle hub are releasably connected and when they
are connected, the insertion needle is placed along the sensor
(e.g. surrounding the sensor wholly or partly). The carrier body
guides the movement relative to the housing between a retracted and
an advanced position. When released, the needle unit and the sensor
housing are forced by a spring unit to an advanced position where
the needle and sensor are placed subcutaneously. Upwardly-bent
parts on the leg of the housing set the insertion angle of about
30.degree. into the skin of the patient.
[0009] U.S. Patent Application Publication 2012/0226122 (2012,
Meuniot et al.) discloses an inserter device for an analyte sensor.
The device includes a housing that is positioned above the
subcutaneous fat layer, a blade shuttle, and a sensor shuttle. A
spring is compressed between the blade shuttle and the sensor
shuttle. The blade shuttle and sensor shuttle move towards the
subcutaneous fat layer. When a spring force is released by the
spring, the blade shuttle moves towards and pierces into the
subcutaneous fat layer creating a pathway into the subcutaneous fat
layer. The analyte sensor is implanted by the sensor shuttle by
following the blade shuttle into the pathway created by the blade
shuttle. The blade shuttle is then retracted from the subcutaneous
fat layer, leaving the analyte sensor in the fat layer.
[0010] U.S. Patent Application Publication 2013/0256289 (2013,
Hardvary et al.) discloses a diagnostic device. The diagnostic
device has partially retractable hollow guide needles for the
intradermal placement of diagnostic elements fixedly connected to
measuring means within this device. This obviates the need to
remove the guide needle and to connect the diagnostic elements to
the measuring means after placement into the skin.
SUMMARY OF THE INVENTION
[0011] Continuous glucose monitoring (CGM) devices have been slow
to be adopted by many patients due to the pain and long term
discomfort of initial deployment and long term use (3 to 7 days).
Currently available devices are commonly compared and criticized on
CGM user forums for their pain of deployment.
[0012] Pain of deployment can be shown to be directly related to
the design of the device. Axons that pass through the subcutaneous
layer and end in the epidermis are called nociceptors. These
specialized neurons transmit pain messages. The density of these
pain receptors ranges between 2 and 2500 neurites/mm.sup.2 just
below the skin surface, and varies greatly depending on location.
The probability and magnitude of a pain response during any
incision is proportional to the number of affected nociceptors and
the trauma inflicted upon these nociceptors. With nociceptors
located throughout the thickness of the epidermis, a deeper
incision is more likely to trigger a pain response due to the
increased likelihood of trauma to more nociceptors.
[0013] When inserted into subcutaneous tissue, the combined cross
sectional area of a sensor and introducer is proportional to the
force of insertion and also to the probability and magnitude of
triggering pain response. FIG. 1 is a graph 10 showing the maximum
peak force 12 of insertion (lbs.) of various commercial inserter
sets plotted against the measured cross section area 14 of the
inserter set (in.sup.2.times.10.sup.-3). As can be seen by a linear
regression of the data points in FIG. 1, the peak force increases
linearly with cross sectional area with a regression line 16
represented by equations 1 and 1a, which have an R.sup.2 value of
0.932. Data in graph 10 is for needles inserted at 90 degrees to
the skin surface regardless of the intended insertion angle of the
particular needle.
peak force (lb.sub.f)=(0.3998)(cross sectional area
(in.sup.2))+0.0556 lb.sub.f (1)
peak force (N)=(0.0223)(cross-sectional area (m.sup.2))+1.100 N
(1a)
[0014] Among the tested needles for graph 10 in FIG. 1 and graph 20
in FIG. 2, Brand A is a 22 gauge split needle with a lumen, Brand B
is a 22-24 gauge needle with a bi-lumen, Brand C is a 23-24 gauge
split needle with a single lumen, and Brand D is a 26 gauge needle.
A split needle means that about a third of the needle is removed
for a distance creating a skive cut in the needle. The Brand A
needle with lumen has the highest peak force. The Brand C needle
has a peak force that is slightly less than the larger 22 gauge
Brand A split needle. The Brand D needle is a needle intended for
insertion at 45 degrees to the skin surface. It is notable that the
peak force increases by 11% when inserting a needle at 45 degrees
compared to 90 degrees to the skin surface. Thus, when used as
intended, the peak force for Brand D needle would be 11% greater
than as shown in FIG. 1.
[0015] It is important to note that the sensor of the present
invention was installed in various needle sizes and tested for peak
insertion force. As can be seen from the graph, the sensor of the
present invention in a 23-gauge split needle has a lower peak
insertion force than the comparable Brand C needle. Also, the
sensor of the present invention in a 24-gauge split needle had a
lower peak insertion force than the Brand D 26-gauge needle
notwithstanding having a larger cross-sectional area than the Brand
D needle. The needle with the lowest peak force (FIG. 1) and lowest
work (FIG. 2) is the sensor of the present invention in a 27 gauge
XTW Skive Cut needle with an oval cross-sectional shape.
[0016] The cross-sectional area of an inserter set (i.e. needle and
sensor) also strongly correlates with the relative intensity of
pain of insertion as reported by users of these devices. The Brand
D device is considered by users as being much more comfortable than
the earlier Brand A system. The present invention the same or a
larger needle gauge has a better (lower) peak insertion force of a
comparable brand needle as seen from FIGS. 1 and 2.
[0017] FIG. 2 is a graph 20 showing work 22 (lb-in) plotted against
the combined cross sectional area 24 (in.sup.2.times.10.sup.-3) of
the sensor and introducer of various commercial introducer sets.
For insertion of a sensor and introducer in combination, the length
or depth of insertion into subcutaneous tissue is proportional to
the work energy (force times distance) and proportional to the
probability and magnitude of triggering pain response from the
user. As can be seen by a linear regression of the data points of
FIG. 2, the work increases linearly with cross sectional area with
a regression line 26 represented by equations 2 and 2a, which have
an R.sup.2 value of 0.9715.
Work (lb-in)=(0.0439)(cross sectional area (in.sup.2))+0.0133
(2)
Work (N-m)=(6.23E-5)(cross-sectional area (m.sup.2))+1.50E-3 N-m
(2a)
[0018] FIG. 3 is a graph 30 with typical force of insertion 32
(lbs.) plotted against insertion distance 34 (in) to demonstrate
the concept of work energy. FIG. 3 is a plot of data obtained from
three separate insertion force measurements for a Brand R inserter
with a Brand R sensor. As the sharp penetrates tissue, the force is
dynamically recorded. The integral of a curve 36 (i.e., the area 28
under one of curves 36a-36c) is the work energy (lb-in). Work
energy (force times distance) is proportional to the incidence of
triggering a pain response by users of the inserter. In simple
terms, small, shallow incisions hurt less for the reasons stated
above. Therefore, an inserter that reduces or minimizes insertion
pain is more likely to be adopted by patients.
[0019] Reducing or minimizing insertion pain is one criterion for
patient acceptance of any continuous monitoring system. Other
criteria include the convenience and ease-of-use of the inserter
device. Therefore, a need exists for an inserter set and an
inserter assembly that reduces or minimizes the patient's pain and
inconvenience of inserting a continuous monitoring sensor. The
present invention achieves these and other objectives by providing
a continuous analyte monitoring inserter apparatus for subcutaneous
placement of a sensor into a patient and a sharp/needle that
minimizes insertion pain with a reduced cross-sectional area.
[0020] In one embodiment of the present invention, a sharp useful
for continuous glucose monitoring has an elongated tubular body
with a pointed tip. The elongated tubular body has a generally oval
or elliptical cross-sectional shape and defines a conduit
therethrough. A sharp open region extends a predefined distance
from the pointed tip along the elongated tubular body and has a
portion of the generally oval tubular body removed, thereby
defining an unenclosed concave well within the remaining elongated
tubular body. In another embodiment, the sharp includes a
continuous monitoring sensor retained in the concave well, where
the top surface of the continuous monitoring sensor resides
completely within the concave well formed by the wall of the
tubular body.
[0021] Another aspect of the present invention is an inserter
assembly. In one embodiment, the inserter assembly is a single
action inserter assembly that, using a single action, substantially
simultaneously performs the steps of (1) implanting the sensor
subcutaneously into the patient, (2) fixedly seating a sensor
deployment assembly that includes the sensor within a sensor
housing attached to the patient, (3) retracting a needle used to
implant the sensor, and (4) releasing the inserter assembly from
the sensor housing. In one embodiment, the action of retracting the
needle is performed by retracting the needle into the inserter
assembly. In another embodiment, the inserter assembly further
includes implanting a lumen along with the sensor subcutaneously in
the patient.
[0022] In another embodiment, the inserter assembly includes a
deployment button containing a needle deployment mechanism. The
needle deployment mechanism has a needle carrier incorporating a
sharp and a needle carrier catch that temporarily prevents the
needle carrier from moving. The deployment button is movably
received in a inserter housing, where the inserter housing has a
sensor deployment assembly that connects in mating agreement to the
sharp. The sharp extends beyond the sensor deployment assembly into
the sensor housing and contains the sensor, which is not fixedly
attached to the sharp. A sensor housing is releasably received
within the inserter housing.
[0023] In another embodiment, the inserter assembly includes an
inserter housing having a first housing end and a second housing
end. A deployment button is at least partially disposed in and
slidable within the inserter housing through the first housing end,
where the deployment button is movable between a first position and
a second position. The second position may be a locked position. A
deployment mechanism slidably disposed within the deployment button
is movable between a ready position, an insertion position, and a
retracted position. The deployment mechanism has a needle.
[0024] A sensor deployment assembly is disposed within the inserter
housing and removably mated with the deployment mechanism and the
deployment button. The sensor deployment assembly has a needle bore
in which the needle is disposed when the deployment mechanism is in
the ready position. A sensor is partially disposed within the
needle or the needle bore, where the deployment mechanism, the
needle, and the sensor define a deployment axis. The sensor has an
electrode system and an electrical contact portion. In one
embodiment, the electrical contact portion is parallel to but
spaced from the deployment axis. In another embodiment, the
electrical contact portion extends transversely away from the
deployment axis. In one embodiment, for example, the electrical
contact portion extends substantially perpendicularly from the
deployment axis.
[0025] The inserter assembly also includes a sensor housing
disposed at and removably retained by the second housing end of the
inserter housing. The sensor housing has a bottom surface that
defines a sensor opening therethrough and aligned with the
deployment axis.
[0026] Movement of the deployment button from the first position to
the second position causes the sensor to be implanted
subcutaneously into the patient along the deployment axis, the
needle of the deployment mechanism to retract to the retracted
position, the sensor deployment assembly to be fixed within the
sensor housing, and inserter assembly to release from the sensor
housing. In one embodiment, the inserter assembly includes the
inserter housing, the deployment button and the deployment
mechanism.
[0027] In some embodiments, the movement of the deployment button
from the first position to the second position is a single movement
causing substantially at the same time the sensor to be implanted
subcutaneously into the patient along the deployment axis, the
needle of the deployment mechanism to retract to the retracted
position, the sensor deployment assembly to be fixed within the
sensor housing, and the inserter housing, the deployment button and
the deployment mechanism to release from the sensor housing.
[0028] In one embodiment, the single activation has an auditory
indication that the sensor is implanted in the patient and the
inserter assembly is released from the sensor housing. In another
embodiment, the single activation has a sensory indication through
the inserter assembly that the sensor is implanted in the patient
and the inserter assembly is released from the sensor housing.
[0029] In another embodiment, the inserter housing has a housing
recess for receiving and retaining a button catch when the
deployment button is in the second position.
[0030] In another embodiment, the inserter housing has a body catch
retaining the sensor housing partially within the inserter housing.
The body catch is released from the sensor housing by the
deployment button when the deployment button is moved into the
second position.
[0031] In another embodiment, the sensor deployment assembly
includes a sensor deployment body, a sensor deployment guide, and a
sensor carrier. The sensor deployment body has a sensor deployment
locking mechanism configured to engage the sensor housing when the
button is moved to the second locked position, thereby locking the
sensor deployment assembly with the sensor housing. In one
embodiment, the sensor deployment locking mechanism is one or more
resilient deployment catches on the sensor deployment assembly
biased to engage a deployment catch surface on the sensor housing.
Similarly, the deployment locking mechanism may be one or more
resilient deployment catches on the sensor housing that are biased
to engage respective deployment catch surfaces on the sensor
deployment assembly.
[0032] The sensor deployment guide is attached to the sensor
deployment body and positioned to stop travel of the deployment
assembly when the deployment button is moved to the second locked
position. For example, the deployment guide contacts the sensor
housing to stop travel of the deployment assembly. The sensor
carrier is attached to the sensor deployment guide, secures the
sensor, and has a board-receiving face.
[0033] In some embodiments, the sensor deployment assembly further
includes a plurality of electronic coupling pads electrically
coupled to the electrical contact portion of the sensor. The
electronic coupling pads are positioned to be electrically coupled
to measuring electronics.
[0034] In some embodiments, the sensor deployment assembly defines
a sensor groove along the top sensor carrier surface, where the
sensor extends through the sensor groove on its way to the
electronic coupling pads attached to an upper deployment body.
[0035] In some embodiments, the deployment axis is substantially
perpendicular to the bottom surface of the sensor housing, where
the bottom surface of the sensor housing is configured to contact
the patient during implantation of the sensor.
[0036] In yet other embodiments, the inserter assembly includes an
electrical component housing that is releasably attachable to the
sensor housing and configured to receive and transmit electrical
signals generated by the electrode system on the sensor.
[0037] In other embodiments, the inserter assembly includes a cover
assembly that is releasably attachable to a top of the sensor
deployment assembly. The cover assembly has a sensor housing
engagement mechanism configured to engage the sensor housing to
lock the cover assembly to the sensor housing. A sealing member on
a bottom surface of the cover assembly aligns with and forms a seal
between the delivery bore and the needle bore. A sensor board with
electronic coupling pads is electrically coupled to the electrical
contact portion of the sensor, where the sensor mates with the
electronic coupling pads positioned for being electrically coupled
to measuring electronics. The cover assembly also includes an
electrical component configured to receive and transmit electrical
signals generated by the electrode system on the sensor. The
electrical component has electrical contacts coupled to the
electronic coupling pads on the sensor deployment assembly.
[0038] In other embodiments, the inserter assembly includes a
resilient button catch on the inserter housing or the sensor
housing, where the button catch is biased to engage a button catch
surface on the other of the inserter housing or the sensor housing
when the deployment button is in the second position. The inserter
assembly may also include a resilient needle-carrier catch on the
deployment button or the needle carrier, where the needle-carrier
catch is biased to disengage a second catch surface on the other of
the deployment button or the needle carrier when the deployment
button is moved to the second position. The inserter assembly may
also include a resilient housing catch on the inserter housing or
the sensor housing, where the housing catch is biased to disengage
a housing catch surface on the other of the inserter housing or the
sensor housing when the button in moved to the second position.
[0039] Another embodiment of the inserter assembly has an inserter
housing with a housing circumferential wall defining a wall inside
surface, a first housing end and a second housing end. The housing
circumferential wall has at least one of either a cam surface
extending longitudinally along a portion of the wall inside surface
from a first point spaced from the first housing end to a second
point spaced from the second housing end or a cam rider adapted for
sliding along a cam surface. When the housing circumferential wall
has the cam surface, the cam surface causes a wall thickness of the
housing circumferential wall along the at least one cam surface to
become thinner from the first point to the second point.
[0040] The inserter assembly also has a deployment button with a
button circumferential wall defining a wall outside surface, a
first button end and a second button end. The button
circumferential wall has at least one of either a resilient cam
rider adapted for sliding along the at least one cam surface of the
housing circumferential wall when the inserter housing has the at
least one cam surface, or a cam surface extending longitudinally
along a portion of a button outside wall surface when the inserter
housing has a cam rider. The deployment button is at least
partially disposed in and slidable within the inserter housing
through the first housing end, where the second button end is
inside the inserter housing and the first button end is outside the
inserter housing. The deployment button is movable only between a
first position, where a larger portion of the button
circumferential wall is outside of the inserter housing, and a
second position, where a smaller portion of the button
circumferential wall is outside of the inserter housing.
[0041] The inserter assembly also has a needle assembly that
includes an assembly body with a needle body end and a hollow
needle with a longitudinal slot through a needle circumferential
wall. The hollow needle is fixedly attached to the needle body end.
The needle assembly is slidably disposed within the deployment
button and movable only between a ready position and a retracted
position. When the needle assembly is in the ready position, the
hollow needle extends out of the second button end of the
deployment button.
[0042] The inserter assembly also has a sensor deployment assembly
detachably mated with the deployment button at the second button
end. The sensor deployment assembly has a needle bore through which
the hollow needle extends when the needle assembly is in the ready
position. The sensor deployment assembly also has a sensor with an
electrode end portion and a sensor electrical contact portion. The
sensor is partially disposed within the needle bore and within the
hollow needle, where the sensor is adapted to provide a lateral
force against the needle circumferential wall when the needle
assembly is in the ready position and during insertion of the
sensor subcutaneously. The sensor electrical contact portion
extends laterally away from the needle bore and the hollow
needle.
[0043] The inserter assembly also has a sensor housing disposed at
and removably retained by the second housing end of the inserter
housing. The sensor housing has a bottom surface and defines a
sensor opening therethrough that is aligned with the hollow needle
for receiving the hollow needle therethrough.
[0044] Movement of the deployment button from the first position to
the second position causes, in a substantially simultaneous action,
the sensor to be implanted subcutaneously into the patient, the
needle assembly to retract to the retracted position, the sensor
deployment assembly to be fixed within the sensor housing, and the
inserter housing to release from the sensor housing.
[0045] In another embodiment of the inserter assembly, the sensor
deployment assembly includes a lower deployment body and an upper
deployment body. For example, the lower deployment body has a top
surface, a bottom surface, a circumferential surface, a bore
forming a portion of the needle bore, and a slot formed into the
top surface of the lower deployment body and in communication with
the bore, where the slot contains the sensor electrical contact
portion of the sensor. The upper deployment body has a top surface,
a bottom surface, a bore forming a portion of the needle bore, a
plurality of resilient electrical contact members extending above
the top surface and below the bottom surface, and a skirt extending
downward from the bottom surface along a circumferential portion of
the upper deployment body. The skirt extends to at least the bottom
surface of the lower deployment body and is positioned to abut the
sensor housing to stop travel of the sensor deployment assembly
when the deployment button is moved to the second position. The
upper deployment body is fixedly attached to the lower deployment
body, thereby capturing the sensor electrical contact portion in
the slot of the lower deployment body and causing the plurality of
resilient electrical contact members to electrically couple to a
plurality of electrical contact pads on the sensor electrical
contact portion. The sensor deployment assembly has a sensor
deployment locking mechanism configured to engage the sensor
housing when the button is moved to the second position, thereby
locking the sensor deployment assembly within the sensor
housing.
[0046] In another embodiment of the inserter assembly, the bottom
surface of the sensor housing is configured to adhere to the
patient during implantation of the sensor. In one embodiment, for
example, the sensor deployment locking mechanism includes one or
more bores with a resilient deployment catch extending upward from
an inside bottom surface of the sensor housing, where the resilient
deployment catch is biased to engage a deployment catch surface of
the one or more bores in the sensor deployment assembly.
[0047] In another embodiment of the inserter assembly, the sensor,
when implanted subcutaneously in the patient, has a working
electrode of an electrode system on the sensor extending into the
patient by about 4 mm to about 7 mm. In another embodiment, the
sensor, when implanted subcutaneously in the patient, has a working
electrode of an electrode system on the sensor extending into the
patient by about 2 mm to about 10 mm.
[0048] In another embodiment, the inserter assembly also includes a
resilient button catch on one of the inserter housing or the sensor
housing, where the button catch is biased to engage a button catch
surface on the other of the inserter housing or the sensor housing
when the deployment button is in the first position. The deployment
button or the needle carrier has a resilient needle assembly catch
biased to disengage a second catch surface on the other of the
deployment button or the needle assembly when the deployment button
is moved to the second position. One of the inserter housing or the
sensor housing has a resilient housing catch biased to disengage a
housing catch surface on the other of the inserter housing or the
sensor housing when the deployment button is moved to the second
position.
[0049] In some embodiments of the sensor inserter assembly, the
movement of the deployment button from the first position to the
second position is a single movement causing substantially at the
same time the sensor to be implanted subcutaneously into the
patient, the needle assembly to retract to the retracted position,
the sensor deployment assembly to be fixed within the sensor
housing, and the inserter housing to release from the sensor
housing.
[0050] Another aspect of the present invention is directed to a
multi-layer, thin-film substrate assembly for use in forming a
subcutaneous analyte sensor. In one embodiment, the substrate
assembly has a base layer made of an electrically-insulating
material, where the base layer has a base layer substrate with a
base layer proximal end portion, a base layer distal end portion,
and a base layer middle portion extending longitudinally between
the base layer proximal end portion and the base layer distal end
portion.
[0051] A first metallized layer is disposed on the base layer
substrate and defines at least one circuit extending longitudinally
along the base layer substrate. Each circuit has an
electrically-conductive contact pad formed at each of the base
layer proximal end portion and the base layer distal end portion
with an electrically-conductive trace electrically coupling the
electrically-conductive contact pad at the base layer proximal end
portion with the electrically-conductive pad at the base layer
distal end portion.
[0052] A middle layer is disposed over the base layer, where the
middle layer has a middle layer substrate made of an
electrically-insulating material with a second proximal end
portion, a second distal end portion, and a second middle portion.
The middle layer is aligned with the base layer and has a plurality
of middle layer through openings with side walls. Each of the
middle layer through openings is in communication with a respective
one of the electrically-conductive contact pad of the circuit(s) of
the base layer.
[0053] A second metallized layer is disposed on the middle layer
and the side walls of the through openings. The second metallized
layer defines at least two circuits, where each of the circuits of
the second metallized layer has an electrically-conductive contact
pad formed at the second proximal end portion and at the second
distal end portion with an electrically-conductive trace
electrically coupling the electrically-conductive contact pad at
the middle layer second proximal end portion with the
electrically-conductive pad at the middle layer distal end portion.
One of the circuits is electrically coupled to the circuit(s) of
the base layer by way of the plurality of middle layer through
openings.
[0054] A top layer made of an electrically-insulating material is
disposed over the middle layer. The top layer has a plurality of
contact openings that coincide with each electrically-conductive
contact pad of the middle layer proximal end portion and a
plurality of sensor openings that coincide with each
electrically-conductive contact pad of the middle layer distal end
portion, thereby creating a substrate assembly with an substrate
proximal end portion, an substrate distal end portion and an
assembly middle portion extending longitudinally between the
substrate proximal end portion and the substrate distal end
portion. Each electrically-conductive contact pad at the second
distal end portion is adapted to receive an electrode reagent to
form a respective electrode and each electrically-conductive
contact pad at the second proximal end portion is adapted to
receive an electrical contact.
[0055] In another embodiment, the multi-layer, thin-film substrate
assembly has multiple middle layers.
[0056] In another embodiment, the base layer, the circuit(s) of the
first metallized layer, the middle layer, the middle layer
circuits, and the top layer together impart an arcuate shape to the
substrate assembly from the substrate proximal end portion to the
substrate distal end portion.
[0057] In another embodiment of the substrate assembly, the
electrically insulating material of each of the base layer, the
middle layer, and the top layer is polyimide that is spun-formed
and thermally cured.
[0058] In one embodiment of the substrate assembly, for example,
the base layer and the middle layer have a thickness of about 10
microns. In another embodiment of the substrate assembly, the top
layer has a thickness about five times the thickness of the middle
layer. In another embodiment of the substrate assembly, the top
layer has a thickness of about 55 microns. In another embodiment of
the substrate assembly, the sensor assembly has a thickness of
about 75 microns. In yet another embodiment, each of the substrate
distal end portion and the assembly middle portion has a width of
about 279 microns.
[0059] In another embodiment of the substrate assembly, the first
metallized layer has a thickness in the range of about 900
Angstroms to about 1,500 Angstroms.
[0060] In another embodiment of the substrate assembly, the first
metallized layer and the second metallized layer each includes
gold. In another embodiment, the first metallized layer and the
second metallized layer each includes a layer of chromium disposed
against the base layer substrate and the middle layer substrate,
respectively, and a layer of gold disposed on top of the layer of
chromium. In another embodiment, the second metallized layer
includes a layer of chromium disposed against the middle layer
substrate, a layer of gold disposed on top of the layer of
chromium, and a layer of platinum disposed on top of the layer of
gold.
[0061] In another embodiment of the substrate assembly, the base
layer has at least two circuits with respective
electrically-conductive pads for each circuit at the base layer
proximal end portion and the base layer distal end portion. The
middle layer has at least two second-layer circuits with
electrically-conductive pads for each second-layer circuit at the
middle layer proximal end portion and the middle layer distal end
portion. In one embodiment, for example, the first metallized layer
of the base layer includes at least two additional
electrically-conductive contact pads at the base layer distal end
portion that aligns and coincides with the electrically-conductive
pads at the middle layer distal end portion.
[0062] Another aspect of the present invention is directed to an
electrochemical sensor assembly for use as a subcutaneous analyte
sensor. In one embodiment, the electrode assembly has a base layer
with a base layer substrate of electrically-insulating material
that defines a base layer proximal end portion, a base layer distal
end portion, and a base layer middle portion between the base layer
proximal end portion and the base layer distal end portion. The
base layer also has a first metallized layer disposed on the base
layer substrate and defining at least one circuit extending
longitudinally along the base layer substrate. Each circuit has an
electrically-conductive contact pad formed at each of the base
layer proximal end portion and the base layer distal end portion.
An electrically-conductive trace electrically couples the
electrically-conductive contact pad at the base layer proximal end
portion with the electrically-conductive pad at the base layer
distal end portion.
[0063] A middle layer is disposed over the base layer and has a
middle layer substrate of electrically-insulating material. The
middle layer substrate has a middle layer proximal end portion, a
middle layer distal end portion, and a middle layer middle portion,
where the middle layer is aligned with the base layer and has a
plurality of second-layer through openings with side walls. Each of
the plurality of second-layer through openings is in communication
with a respective one of the electrically-conductive contact pad of
the at least one circuit of the base layer. A second metallized
layer is disposed on the middle layer substrate and the side walls
of the second-layer through openings. The second metallized layer
defines at least two circuits, where each of the second-layer
circuits has an electrically-conductive contact pad formed at each
of the middle layer proximal end portion and the middle layer
distal end portion with an electrically-conductive trace
electrically coupling the electrically-conductive contact pad at
the middle layer proximal end portion with the
electrically-conductive pad at the middle layer distal end portion.
One of the at least two second-layer circuits is electrically
coupled to the at least one circuit of the base layer by way of the
plurality of second-layer through openings.
[0064] A top layer of electrically-insulating material is disposed
over the middle layer. The top layer has a plurality of contact
openings that coincide with each electrically-conductive contact
pad of the middle layer proximal end portion and a plurality of
sensor wells that coincide with each of the electrically-conductive
contact pad of the middle layer distal end portion, thereby
creating a substrate assembly with an substrate proximal end
portion, an substrate distal end portion and an assembly middle
portion extending longitudinally between the substrate proximal end
portion and the substrate distal end portion.
[0065] A sensing layer is disposed on at least one
electrically-conductive contact pad formed at the middle layer
distal end portion to form at least a first working electrode. A
reference layer is disposed on at least one electrically-conductive
contact pad formed at the middle layer distal end portion forming a
reference electrode. In another embodiment, there is further
included a counter electrode and at least a second working
electrode (also called a blank electrode because it is used to
measure background current caused by interferents in the sample and
not to measure a specific analyte). In still other embodiments,
there are one or more additional working electrodes adapted to
measure other specific analytes. In one embodiment, the at least
first working electrode is a glucose measuring electrode.
[0066] In one embodiment, sensing layer includes three coating
layers. A base coating later disposed directly on the metallized
pad use to form a working electrode that contains PHEMA and glucose
oxidase and/or glucose dehydrogenase, a second coating layer
disposed directly on the base coating layer that contains PHEMA and
a plurality of microspheres made of a material having substantially
no or little permeability to glucose but a substantially high
permeability to oxygen, and a third coating layer over the second
coating layer, the third coating layer containing PHEMA and a
material that prevents release of hydrogen peroxide from the
sensing layer. In one embodiment, the microspheres are made from
polydimethylsiloxane. In one embodiment, the third coating layer
contains catalase.
[0067] In another embodiment, the base coating layer contains
PHEMA, glucose oxidase and/or glucose dehydrogenase and a quantity
of microspheres that is less that the quantity of microspheres in
the second coating layer.
[0068] In another embodiment of the electrochemical sensor
assembly, the base layer, the at least one circuit, the middle
layer, the at least second-layer one circuit, and the top layer
together impart an arcuate shape to the substrate assembly from the
substrate proximal end portion to the substrate distal end
portion.
[0069] In another embodiment of the electrochemical sensor
assembly, each of the base layer substrate, the middle layer
substrate, and the top layer substrate are polyimide that is
spun-formed and thermally cured.
[0070] In another embodiment of the electrochemical sensor
assembly, the base layer substrate and the middle layer substrate
each have a thickness of about 10 microns. In another embodiment,
the top layer has a thickness about five times the thickness of the
middle layer substrate. In another embodiment, the top layer has a
thickness of about 55 microns. In another embodiment, the sensor
assembly has a thickness of about 75 microns. In another
embodiment, each of the substrate distal end portion and the
assembly middle portion has a width of about 279 microns.
[0071] In another embodiment of the electrochemical sensor
assembly, the first metallized layer has a thickness in the range
of about 900 Angstroms to about 1,500 Angstroms. In one embodiment,
the first metallized layer and the second metallized layer each
includes gold. In another embodiment, the first metallized layer
and the second metallized layer each includes a layer of chromium
disposed against the base layer substrate and the middle layer
substrate, respectively, and a layer of gold disposed on top of the
layer of chromium.
[0072] In another embodiment of the electrochemical sensor
assembly, the second metallized layer includes a layer of chromium
disposed against the middle layer substrate, a layer of gold
disposed on top of the layer of chromium, and a layer of platinum
disposed on top of the layer of gold.
[0073] In another embodiment of the electrochemical sensor
assembly, the base layer includes at least two circuits, where one
electrically-conductive pad with the sensing layer at the middle
layer distal end portion forms a working electrode circuit, and
where a second electrically-conductive pad at the middle layer
distal end portion forms a blank electrode.
[0074] In another embodiment of the electrochemical sensor
assembly, the base layer has at least two circuits and the middle
layer has at least 2 circuits with respective
electrically-conductive pads for each circuit at the respective
distal end portion and the proximal end portion. In another
embodiment, the first metallized layer of the base layer includes
at least two additional electrically-conductive contact pads at the
base layer distal end portion that align and coincide with the
electrically-conductive pads at the middle layer distal end
portion.
[0075] In another embodiment of the present invention, there is
discloses a continuous glucose monitoring system. The system has an
inserter assembly, a sensor housing cover assembly, and an
electronic device. The inserter assembly has an inserter housing, a
deployment button disposed within the inserter housing such that
the deployment button is slidable from a first position to a second
position only for deployment of a subcutaneous sensor into
subcutaneous tissue through the skin, and a sensor housing for
receiving and capturing a sensor deployment assembly from the
deployment button where the sensor deployment assembly has a
subcutaneous sensor. The sensor housing cover assembly configured
for attachment to the sensor housing after insertion of the
subcutaneous sensor where the cover assembly has an electronic
module positioned for electronic coupling to the subcutaneous
sensor and capable of storing and transmitting calculated data
based on the input signals from the sensor. The electronic device
is equipped with wireless communication for communicating with the
electronic module of the sensor housing cover assembly. The
electronic device having electronic circuits and software for
receiving input signals from the sensor, converting the input
signals to analyte data, displaying the analyte data on a user
interface of the electronic device, storing the data for recall,
and creating and/or sending reports of the data.
[0076] In another embodiment, the sensor of the continuous glucose
monitoring system has a base layer with a base electrical circuit,
a middle layer with middle electrical circuit where the middle
layer has openings to the base layer electrically connecting
portions of the middle electrical circuit with portions of the base
electrical circuit.
[0077] In another aspect of the invention, a method of inserting an
in-vivo analyte sensor subcutaneously for continuous analyte
monitoring of a patient includes the steps of providing a single
action inserter assembly having a needle, an implantable sensor, a
deployment button for implanting the implantable sensor using the
needle and for retracting the needle, and a sensor housing for
retaining the implanted sensor in an implanted orientation once
deployed by the deployment button; and using a single action to
activate the deployment button of the single action inserter
assembly that causes the following actions to substantially
simultaneously occur: (1) implanting the sensor subcutaneously into
the patient, (2) fixedly seating the sensor within the sensor
housing attached to the patient, (3) retracting the needle into the
inserter assembly, and (4) releasing the inserter assembly from the
sensor housing.
[0078] In another embodiment of the method, the providing step
includes providing a single action inserter assembly that has a
lumen disposed on the needle and the using step includes implanting
the lumen subcutaneously into the patient with the sensor and
fixedly seating the lumen within the sensor housing attached to the
patient.
[0079] In another aspect of the present invention, a continuous
analyte monitoring inserter apparatus for subcutaneous placement of
a sensor into skin of a patient minimizes pain to a patient. In one
embodiment, the apparatus has a single action inserter assembly
having a inserter housing with a first housing end and a second
housing end. A deployment button is partially disposed in and
slidable within the inserter housing through the first housing end,
where the deployment button being movable between a first position
and a second position. A sensor housing is partially disposed
within and removably retained in the second housing end. A needle
is movably disposed within the single action inserter assembly. The
needle has a cross-sectional shape that minimizes a peak force of
insertion into the skin of the patient. An implantable sensor is
partially disposed within the needle. The inserter assembly is
adapted to substantially simultaneously implant the sensor
subcutaneously into the patient, retract the needle, fix the sensor
within the sensor housing and release the inserter assembly from
the sensor housing with a single activation of the deployment
button caused by moving the deployment button from the first
position to the second position while minimizing pain to the
patient.
[0080] In another embodiment, a longitudinal portion of the needle
has a skive cut along a length of the needle from a sharp end of
the needle to a predefined location.
[0081] In another embodiment, the needle is oriented substantially
perpendicular to a surface of the single action inserter, where the
surface is a portion of the sensor housing and intended for
placement against the skin of the patient.
[0082] In another embodiment, the needle has a cross-sectional
shape of an oval, an ellipse, an egg-shape, or an oblong shape. In
another embodiment, the longitudinal portion of the needle has a
cross-sectional shape of an oval, an ellipse, an egg-shape, or an
oblong shape.
[0083] In another aspect of the present invention is a method of
minimizing pain when inserting an in-vivo analyte sensor
subcutaneously for continuous analyte monitoring of a patient. In
one embodiment, the method includes providing a single action
inserter assembly having a needle with a cross-sectional shape that
minimizes a peak force of insertion into the skin of the patient,
an implantable sensor, a deployment button for implanting the
implantable sensor using the needle and for retracting the needle,
and a sensor housing for retaining the implanted sensor in an
implanted orientation once deployed by the deployment button; and
using a single action to activate the deployment button of the
single action inserter assembly that causes the following actions
to substantially simultaneously occur: (1) implanting the sensor
subcutaneously into the patient, (2) fixedly seating the sensor
within the sensor housing attached to the patient, (3) retracting
the needle used to implant the sensor into the inserter assembly,
and (4) releasing the inserter assembly from the sensor housing,
wherein the needle and the single action minimizes pain when
inserting the sensor subcutaneously.
[0084] In another embodiment of the method, the providing step
includes providing a needle with a skive cut along a longitudinal
portion of the needle from a sharp end of the needle to a
predefined location along the length of the needle.
[0085] In another embodiment of the method, the providing step
includes providing a needle that is oriented substantially
perpendicular to a surface of the single action inserter, where the
surface is a portion of the sensor housing and intended for
placement against the skin of the patient.
[0086] In another embodiment of the method, the providing step
includes providing a needle with an oval, elliptical, egg-shaped,
or oblong cross-sectional shape. In another embodiment of the
method, the providing step includes providing a needle with the
longitudinal portion having an oval, elliptical, egg-shaped, or
oblong cross-sectional shape.
[0087] In another aspect of the present invention, a method of
making a sharp includes providing a longitudinal tubular body
having a first end and a second end; compressing the longitudinal
tubular body to have a substantially oval and/or elliptical
cross-sectional shape; removing a portion of the tubular body
proximate the first end and extending a predefined distance towards
the second end where the portion is parallel to a major axis of the
oval/elliptical cross-sectional shape; and forming a sharp tip on
the first end.
[0088] In yet another aspect of the present invention, a method of
continuous analyte monitoring includes placing an inserter assembly
on an insertion site of a patient. The inserter assembly has a
sensor carrier, an inserter set with a sharp and an analyte sensor,
and a deployment assembly. The deployment assembly includes a
deployment button, a inserter housing, and a deployment mechanism.
The method also includes the steps of pressing the deployment
button of the introducer set, thereby deploying the introducer set
into subcutaneous tissue of the patient; retracting the deployment
assembly and removing the sharp from the patient while leaving the
analyte sensor deployed in the sensor carrier and in the patient;
and removing the deployment assembly from the sensor carrier.
[0089] Another aspect of the present invention is directed to a
method of forming a multi-layer, thin-film substrate assembly for
use in forming a subcutaneous analyte sensor. In one embodiment,
the method includes the steps of spin forming and thermally curing
a polyimide base layer substrate into an elongated shape having a
base layer proximal end portion, a base layer distal end portion
and a base layer middle portion between the base layer proximal end
portion and the base layer distal end portion; depositing a first
metallized layer on the base layer substrate defining at least one
circuit extending longitudinally along the base layer substrate,
where the at least one circuit has an electrically-conductive
contact pad formed at each of the base layer proximal end portion
and the base layer distal end portion with an
electrically-conductive trace electrically coupling the
electrically-conductive contact pad at the base layer proximal end
portion with the electrically-conductive pad at the base layer
distal end portion; spin forming and thermally curing a polyimide
middle layer substrate on the first metallized layer and the base
layer substrate aligned with the base layer substrate, where the
middle layer substrate defines a middle layer proximal end portion,
a middle layer distal end portion and a middle layer middle portion
between, where the middle layer proximal end portion and the middle
layer distal end portion define a plurality of second-layer through
openings having side walls, and where each of the plurality of
second-layer through openings is in communication with a respective
one of the electrically-conductive contact pad of the at least one
circuit of the base layer; depositing a second metallized layer on
the middle layer substrate and the side walls of the second-layer
through openings to thereby define at least two circuits, where
each circuit has an electrically-conductive contact pad formed at
each of the middle layer proximal end portion and the middle layer
distal end portion with an electrically-conductive trace
electrically coupling the electrically-conductive contact pad at
the middle layer proximal end with the electrically-conductive pad
at the middle layer distal end portion, and where the at least one
circuit is electrically coupled to the at least one circuit of the
base layer by way of the plurality of second-layer through
openings; and spin forming and thermally curing a polyimide top
layer over the middle layer substrate and the second metallized
layer, where the top layer defines a plurality of openings that
coincide with each electrically-conductive pad of the middle layer
to thereby create a substrate assembly with an substrate proximal
end portion, an substrate distal end portion, and an assembly
middle portion extending longitudinally between the substrate
proximal end portion and the substrate distal end portion, and
where each electrically-conductive contact pad at the middle layer
distal end portion is adapted to receive an electrode reagent to
form a respective electrode and each electrically-conductive
contact pad at the middle layer proximal end portion is adapted to
receive an electrical contact.
[0090] In one embodiment, a method of inserting a sensor
subcutaneously is disclosed. The method includes providing an
inserter assembly containing a sensor and an insertion needle
adapted for implanting the sensor into subcutaneous tissue wherein
the inserter assembly requires a user-perpetrated initial applied
force of greater than 1.5 lbs. that is followed by a decrease in
applied force to an applied force of less than 1.5 lbs, placing the
inserter assembly against a patient's skin, actuating the inserter
assembly to thereby implant the sensor subcutaneously and
disengaging a sensor housing containing the implanted sensor from
the inserter assembly, and removing the inserter assembly from the
patient's skin. In this embodiment, the removed inserter assembly
is the actuation assembly.
[0091] In another embodiment, the providing step includes an
inserter assembly that requires a user-perpetrated initial applied
force in the range of 1.5 to 2.5 lbs. followed by a decrease in the
applied force for insertion of the needle into the subcutaneous
tissue wherein the applied force of the insertion needle is in the
range of about 0.5 lbs to about 1.3 lbs.
[0092] In one embodiment, a method of inserting a sensor
subcutaneously is disclosed. The method includes providing an
inserter assembly containing a sensor and an insertion needle
adapted for implanting the sensor into subcutaneous tissue wherein
the inserter assembly is adapted to insert the sensor into the
subcutaneous tissue and release a post-actuation assembly after
implantation in less than one second, placing the inserter assembly
against a patient's skin, actuating the inserter assembly to
thereby implant the sensor subcutaneously and disengaging a
post-actuation inserter assembly in less than one second, and
discarding the post-actuation inserter assembly.
[0093] In another embodiment, the providing step includes providing
an inserter assembly capable of implanting the sensor
subcutaneously and releasing the post-actuation assembly after
implantation in a time period that is less than 0.5 seconds, a
range of less than 0.25 seconds to 0.8 seconds, a range of less
than 0.5 seconds to 0.8 seconds, a range of 0.5 seconds to 0.8
seconds, a range of 0.25 seconds to 0.5 seconds, and 0.5
seconds.
[0094] In another embodiment, the actuation step includes
implanting the sensor subcutaneously and disengaging the
post-actuation inserter assembly in a time period of less than 0.5
seconds, a range of less than 0.25 seconds to 0.8 seconds, a range
of less than 0.5 seconds to 0.8 seconds, a range of 0.5 seconds to
0.8 seconds, a range of 0.25 seconds to 0.5 seconds, and 0.5
seconds.
BRIEF DESCRIPTION OF THE DRAWINGS
[0095] FIG. 1 is a graph showing insertion force data for various
commercial inserter sets of the prior art, where maximum peak force
of insertion is plotted against the measured cross sectional area
of the inserter set.
[0096] FIG. 2 is a graph showing data for various commercial
inserter sets of the prior art, where the work of insertion is
plotted against the measured cross sectional area of the inserter
set.
[0097] FIG. 3 is a graph showing data for one inserter set of the
prior art, where insertion force is plotted against the distance of
insertion and where the area under a curve is the work energy.
[0098] FIG. 4 is a perspective view of one embodiment of a sharp of
the present invention showing the sharp tip, a sharp open region,
and a portion of the sharp body.
[0099] FIG. 5 is an end perspective view of the sharp of FIG. 4
showing the concave well defined by the sharp open region.
[0100] FIG. 5A is a diagram representing the cross-sectional area
of the sharp open region of the sharp of FIG. 5 with a sensor
disposed in the concave well.
[0101] FIG. 6 is a graph showing data for one inserter set of the
present invention, where insertion force is plotted against the
distance of insertion and where the area under a curve is the work
energy.
[0102] FIG. 7 is a perspective view of one embodiment of a CGM
system of the present invention showing a sensor inserter assembly,
a sensor housing cover and display modules.
[0103] FIG. 8 is a perspective view of the inserter assembly of
FIG. 7.
[0104] FIG. 9 is a cross-sectional side view of the inserter
assembly of FIG. 8.
[0105] FIG. 10 is an exploded perspective view of the inserter
assembly of FIG. 8.
[0106] FIG. 10A is an exploded side view of the sensor inserter
assembly of FIG. 8.
[0107] FIG. 11 is a side view of the deployment button assembly of
the inserter assembly of FIG. 8 showing the deployment button, the
needle assembly and the sensor deployment assembly assembled for
use.
[0108] FIG. 12 is a front view of the deployment button assembly of
FIG. 11.
[0109] FIG. 13 is a cross-sectional side view of the deployment
assembly of FIG. 11.
[0110] FIG. 14 is a cross-sectional front view of the deployment
button assembly of FIG. 12.
[0111] FIG. 15 is a side view of the inserter housing assembly of
the inserter assembly of FIG. 8 showing the inserter housing and
the sensor housing.
[0112] FIG. 16 is a front view of the inserter housing assembly of
FIG. 15.
[0113] FIG. 17 is a cross-sectional side view of the inserter
housing assembly of FIG. 15 showing the inserter housing with one
or more cam surfaces and the sensor housing.
[0114] FIG. 18 is a cross-sectional view of the inserter housing
assembly of FIG. 16 showing the bendable and resilient sensor
housing retaining members.
[0115] FIG. 19 is a cross-sectional side view of one embodiment of
the inserter assembly showing a sensor housing, inserter housing, a
needle assembly, a sensor deployment assembly, a deployment button,
and a deployment button cover.
[0116] FIG. 20 is a top view of a deployment button within an
inserter housing showing a view line 21-21 through one of the cam
surfaces.
[0117] FIG. 21 is a cross-sectional view of the deployment button
and the inserter housing taken alone the view line 21-21 in FIG.
20.
[0118] FIG. 22 is an enlarged view of the cam surface and
deployment button retaining member outlined in FIG. 21.
[0119] FIG. 23 is a graph showing force versus distance for five
samples with needles of the inserter with the cam surface being
deployed into synthetic skin.
[0120] FIG. 24 is a graph showing force versus distance for sample
1 of FIG. 23.
[0121] FIG. 25 is a graph showing force versus distance for sample
2 of FIG. 23.
[0122] FIG. 26 is a graph showing force versus distance for sample
3 of FIG. 23.
[0123] FIG. 27 is a graph showing force versus distance for sample
4 of FIG. 23.
[0124] FIG. 28 is a graph showing force versus distance for sample
5 of FIG. 23.
[0125] FIG. 29 is a cross-sectional side view of the inserter
assembly showing the needle and sensor in an inserted position.
[0126] FIG. 30 is a top view of a deployment button within an
inserter housing showing a view line 31-31 through one of the cam
surfaces of FIG. 30.
[0127] FIG. 31 is a cross-sectional view of the deployment button
and the inserter housing taken alone the view line 31-31 in FIG.
30.
[0128] FIG. 32 is an enlarge view of the cam surface and deployment
button retaining member outlined in FIG. 31.
[0129] FIG. 33 is a cross-sectional side view of an inserter
assembly showing the needle assembly retracted back into the
deployment button.
[0130] FIG. 34 is a cross-sectional front view of the inserter
assembly showing the sensor deployment assembly retaining member in
a released position.
[0131] FIG. 35 is a cross-sectional front view of the inserter
assembly showing a sensor housing retaining member having captured
the sensor deployment assembly within the sensor housing.
[0132] FIG. 36 is a cross-sectional front view of the inserter
assembly showing the inserter housing retaining members in a
released position with the sensor housing caused by the deployment
button.
[0133] FIG. 37 is a perspective top view of the sensor housing with
the sensor deployment assembly captured in the sensor housing after
release of the inserter housing.
[0134] FIG. 38 is a cross-sectional side view of the sensor housing
of FIG. 37.
[0135] FIG. 39 is a perspective bottom view of one embodiment of a
sensor housing cover showing the electronic module and battery
attached to the inside of the sensor housing cover.
[0136] FIG. 40 is a perspective top view of the sensor housing
cover in FIG. 37 connected to the sensor housing after deployment
of the sensor forming the CGM assembly.
[0137] FIG. 41 is a cross-sectional side view of the CGM assembly
of FIG. 40.
[0138] FIG. 42 is a perspective view of one embodiment of a
multi-layer sensor of the present invention.
[0139] FIG. 43 is an exploded perspective view of the multi-layer
sensor of FIG. 42.
[0140] FIG. 44 is a plan view of the sensor of FIG. 42 showing the
base layer only with an electrical contact portion and a sensor end
portion circled.
[0141] FIG. 45 is an enlarged view of the electrical contact
portion of FIG. 44.
[0142] FIG. 46 is an enlarged view of the sensor end portion of
FIG. 44.
[0143] FIG. 47 is a plan view of the sensor of FIG. 42 showing the
middle layer only with an electrical contact portion and a sensor
end portion circled.
[0144] FIG. 48 is an enlarged view of the electrical contact
portion of FIG. 47.
[0145] FIG. 49 is an enlarged view of the sensor end portion of
FIG. 47.
[0146] FIG. 50 is a cross-sectional enlarged view of one of the
electrical contact pads showing the electrically conductive via
from the middle layer to the base layer.
[0147] FIG. 51 is a schematic illustration of the CGM system of the
present invention in use.
[0148] FIG. 52 is an enlarged, side view of one embodiment of the
multi-layer sensor of the present invention showing the curl or
bend of the sensor.
[0149] FIG. 53 is a flow chart showing the steps of the process
that occurs when an inserter assembly of the present invention is
used to implant an analyte sensor subcutaneously in a patient.
[0150] FIG. 54 is a flow chart showing the steps of the process of
making the sensor of the present invention.
[0151] FIG. 55 is a flow chart showing the steps of the process of
depositing the reagent layers onto the sensor substrate forming the
functional electrodes of the sensor.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0152] Exemplary embodiments of the present invention are
illustrated in FIGS. 4-55. FIGS. 4 and 5 illustrate perspective
views of one embodiment of a needle/sharp 100 of the present
invention. Needle/sharp 100 includes a sharp body 102, a sharp open
region 104, and a sharp tip 106. Sharp body 102 is an annular
section of sharp 100 that extends longitudinally and defines an
enclosed conduit 101 therethrough. In one embodiment, sharp 100 is
made from 27 gauge XTW stainless tubing having an outside diameter
of about 0.016 inch (0.41 mm) nominal and an inside diameter of
about 0.012 inch (0.30 mm) nominal. The tubing is then flattened to
have an oval or elliptical shape with an outside height 108 along
the minor axis of the oval or elliptical shape of about 0.0120 inch
(0.30 mm). With the new sensor fabrication discussed later, it is
possible that a smaller sharp 100 made from 28 gauge XTW stainless
steel tubing having an outside diameter of about 0.014 inch (0.36
mm) nominal and an inside diameter of about 0.011 inch (0.28 mm)
nominal.
[0153] A wire EDM machining operation or a laser operation is used
to remove a portion of the tubing wall 103 along sharp 100 a
predefined distance to define sharp open region 104, thereby
reducing the overall height 110 of sharp 100 along the minor axis
of the oval or elliptical shape at sharp open region 104 to about
0.008 inches (0.20 mm). Both the wire EDM machining operation and
the laser operation can be performed on cylindrical tubing or on
flattened, oval tubing as described above. Sharp open region 104 is
a section of an annulus that extends longitudinally with the tubing
wall 103 along the length of sharp open region 104 defining an
unenclosed concave well 114 from sharp tip 106 to sharp body
102.
[0154] Concave well 114 is sized to receive a continuous monitoring
sensor 120. In one embodiment, concave well 114 is sized to receive
a continuous monitoring sensor 120 having a size up to about 0.011
(0.28 mm) wide by about 0.003 (0.075 mm) thick. In one embodiment,
a continuous monitoring sensor top surface 122 (not shown) is
positioned flush with or below a top surface 116a of tubing wall
116 along sharp open region 104. The incision of such a sharp and
sensor combination has a cross sectional area 112 of about
1.33.times.10.sup.-3 in.sup.2 (0.81 mm.sup.2), where cross
sectional area 112 is defined within outside surface 100a of tubing
wall 103 and top surface 116a of tubing wall 116 at sharp open
region 104 (also shown in FIG. 5A). Having continuous monitoring
sensor 120 disposed in concave well 114 of sharp 100 minimizes the
combined cross sectional area of the sharp and sensor as compared
to cylindrical sharps of the same tubing or cylindrical sharps with
a sharp open region but a continuous monitoring sensor that extends
out of the sharp open region. Thus, the insertion force for sharp
100 with continuous monitoring sensor 120 is considerably lower
than the insertion force of prior art insertion sets.
[0155] Referring now to FIG. 6, a plot 80 shows insertion force
data for inserter set 200 of the present invention with force of
insertion 82 plotted vs. the distance 84 of insertion. Each of
plotted lines 86 in FIG. 6 represents a separate measurement at a
different, nearby insertion site. The force of insertion 82 (lb) is
plotted against the distance or depth of insertion 84 (inches). As
shown in FIG. 6, the force of insertion 82 is substantially
constant with only modest increases beyond a depth 84 of about 0.1
inches (2.5 mm), even when the insertion depth 84 is about 0.3
inches (7.6 mm). By inserting sharp 100 in a direction
perpendicular to the tissue surface, inserter set 200 can deposit
continuous monitoring sensor 120 into the critical subcutaneous
layer with minimal trauma to the tissue. The typical insertion
depth during use is from 4 mm to 7 mm for accurate measurement of
subcutaneous glucose. Other inserter designs insert a sharp at
angles of about 45 degrees (more or less) thus increasing length of
insertion by 41%. Work energy (force times distance; the area under
a curve 86) has been shown to be proportional to the incidence of
pain response reported by users.
[0156] To further reduce or minimize the pain of insertion, sharps
100 of the present invention are used in an inserter assembly 200
that deploys continuous monitoring sensor 120 into skin tissue.
Introducer designs that rely on the patient to drive sharp 100 into
the patient's own tissue greatly benefit the patient by providing
low-force and low-work designs. This benefit derives from
psychological reasons as well as from the practical aspect of
having to insert a sharp into a relatively soft abdomen or hip.
[0157] Referring now to FIG. 7, there is illustrated one embodiment
of the CGM system 1000 of the present invention. CGM system 1000
includes an inserter assembly 200, a sensor housing cover assembly
850, and an electronic device 900, 902 that is equipped for
wireless communication. An adhesive component 600, which is
adhesively attached to a bottom of the inserter assembly 200 also
has an adhesive layer on an opposite side of the adhesive component
for adhesively attaching the inserter assembly 200 to the skin of a
patient. Adhesive component 600 may optionally be part of the CGM
system 1000 or a separate component that is attached to the bottom
of inserter assembly 200 only when inserter assembly 200 is about
to be used.
[0158] FIGS. 8 and 9 illustrate perspective and a cross-sectional
views, respectively, of one embodiment of inserter assembly 200 of
the present invention. Inserter assembly 200 includes an inserter
housing 202, a deployment button 204 slidably received in inserter
housing 202, and a sensor housing 206 removably captured by
inserter housing 202. A housing locking mechanism 205 (e.g.,
resilient tab, clip, protrusion, etc.) retains sensor housing 206
captured by inserter housing 202 until deployment of deployment
button 204. Inserter housing 202 has a first housing end 213 and a
second housing end 215 with deployment button 204 at least
partially disposed in and slidable within inserter housing 202
through first housing end 213. A needle assembly 208 is operable
with deployment button 204, inserter housing 202, and sensor
housing 206. Inserter housing 202 includes one or more recesses 212
(not shown) for engagement with deployment button 204 to maintain
deployment button 204 and inserter housing 202 connected to each
other at all times after assembly of inserter assembly 200 and even
after use of inserter assembly 200, as is discussed in more detail
below. The combination of inserter housing 202, deployment button
204, needle assembly 208, button cap 203, and sensor housing 206
form an actuation assembly 201.
[0159] Inserter housing 202 includes at least one first catch
surface 210 (shown in more detail in FIGS. 17 and 22) defined by a
recess, opening, ledge, protrusion, or other structure. First catch
surface 210 is constructed and sized to engage a corresponding
resilient locking catch 214 (shown in FIGS. 11, 12) on deployment
button 204. First catch surface 210 locks deployment button 204
within inserter housing 202 when first assembled and prevents
inadvertent or deliberate separation of deployment button 204 from
inserter housing 202 post assembly. Inserter housing 202 also
includes a second catch surface 210' that is also defined by a
recess, opening, ledge, protrusion, or other structure. Second
catch surface 210' is positioned lower within inserter housing 202
than first catch surface 210. Both first and second catch surfaces
210, 210' are aligned with each other with a housing cam surface
211 formed into a housing wall 218 between each of first and second
catch surfaces 210, 210'. When deployment button 204 is in the
first (ready position), locking catch 214 is held by abutment with
first catch surface 210 of housing wall 218. When the user presses
deployment button 204 down, a tension is initially created in
locking catch 214 by movement of locking catch from first catch
surface 210 onto cam surface 211. Cam surface 211 is configured to
allow locking catch 214 to move outward along cam surface 211
towards its resting, non-tensioned orientation to engage second
catch surface 210'. Of course, inserter housing 202 and deployment
button 204 can be configured so that first and second catch
surfaces 210, 210' are on deployment button 204 and locking catch
214 is on inserter housing 202. Other releasable locking mechanisms
known in the art are also acceptable.
[0160] As can be seen in FIG. 9, deployment button 204 further
includes a needle assembly 208 that is slidably received in a
deployment mechanism cavity 228 in deployment button 204. A
deployment cap 230 closes deployment mechanism cavity 228 to
prevent access to needle assembly 208. Needle assembly 208 includes
a deployment spring 232, a needle/sharp carrier 234 with a needle
carrier catch 235, a hollow, slotted needle 100, and a sensor
deployment assembly 236. Deployment spring 232 (e.g., a coil
spring) is disposed between a spring support component 231 and
needle carrier 234 in a tensioned orientation. Needle carrier catch
235 prevents needle carrier 234 from being moved towards deployment
cap 230 by deployment spring 232. Deployment button 204, needle
assembly 208, deployment cap 230, and inserter housing 202 together
create a cam follower deployment structure 217. When the user
presses deployment button 204, needle carrier catch 235 is released
from a button catch surface 240 by a carrier release surface 203 of
inserter housing 202 and deployment spring 232 then biases needle
carrier 234 towards deployment cap 230.
[0161] FIGS. 10 and 10A are exploded perspective and exploded side
views of inserter assembly 200 showing the various components that
make up inserter assembly 200. Sensor housing 206 is attached to
second housing end 215 of inserter housing 202. An assembly gasket
802 is positioned between a perimeter of sensor housing 206 and
second housing end 215. A sensor housing grommet 251 is attached to
a bottom opening 206b' that receives needle 100 and sensor 120
during subcutaneous insertion of sensor 120. Assembly gasket 802
and grommet 251 are hermetically bonded to sensor housing 206.
Sensor deployment assembly 236 includes a lower deployment body
270, an upper deployment body 236a, a sensor 500 that has a
proximal end portion 501 captured between lower deployment body 270
and upper deployment body 236a, and a distal end portion 502 that
extends through and beyond lower deployment body 270. Sensor
deployment assembly 236 is attached to a second button end 204b,
which is later released and attached to sensor housing 206 during
use. Needle assembly 208 is received within deployment button 204
and retained within deployment button 204 by deployment cap 230.
Needle carrier 234 has at least one, elongated side wing 234a that
slides into a cavity slot 228a of deployment mechanism cavity 228
to prevent needle assembly 208 and needle 100 from rotating within
deployment mechanism cavity 228. Needle carrier 234 also includes
at least one needle carrier catch 235.
[0162] FIGS. 11 and 12 are side and front plan views of one
embodiment of a button assembly 220. Button assembly 220 is a
sub-assembly of inserter assembly 200. Button assembly 220 include
deployment button 204, needle assembly 208 received within
deployment button 204, deployment cap 230, and sensor deployment
assembly 236. In this embodiment, locking catch 214 is part of
deployment button 204. Deployment button 204 also includes a sensor
deployment assembly catch 214' that retains sensor deployment
assembly 236 to deployment button 204 within inserter assembly 200
until deployment button 204 is activated.
[0163] FIGS. 13 and 14 are cross-sectional side and front views of
the embodiments shown in FIGS. 11 and 12, respectively. In FIG. 13,
needle assembly 208 is positioned to maintain the compression of
deployment spring 232 while in the ready position. Needle carrier
catch 235 is in a relaxed state and contacts button catch surface
240, which prevents deployment spring 232 from driving needle
carrier 234 up towards deployment cap 230. In FIG. 14, sensor
deployment assembly catch 214' holds sensor deployment assembly 236
against a portion of second button end 204b. In each of FIGS.
11-14, a portion of sensor 500 is disposed within needle 100.
[0164] Turning now to FIGS. 15-18, there is illustrated one
embodiment of an inserter housing assembly 222. FIGS. 15 and 16 are
side and front plan views of inserter housing assembly 222.
Inserter housing assembly 222 includes inserter housing 202, sensor
housing 206 and assembly gasket 802. Housing locking mechanism 205
retains sensor housing 206 at second housing end 202b. FIG. 17
shows a housing cam surface 211 with first catch surface 210 and
second catch surface 210' where housing cam surface 211 extends
between first and second catch surfaces 210, 210'. The relationship
of housing cam surface 211, first catch surface 210 and second
catch surface 201' with deployment button 204 is more clearly
described later with respect to FIGS. 19-26 as well as the
interactions of the various locking/holding/releasing structures of
inserter assembly 200. FIG. 18 more clearly shows housing locking
mechanism 205 in its normal position with a locking mechanism end
catch 205a retaining sensor housing 206 where locking mechanism end
catch 205a interacts with a sensor housing catch surface 206a. Also
illustrated is a sensor deployment assembly retaining component 217
that is integral with and unitarily formed with sensor housing
206.
[0165] FIG. 19 is an enlarged, cross-sectional, side view of
inserter assembly 200 in a ready-to-use position. This figure is of
particular interest because it can be seen that sensor 500 is
disposed within needle 100 and needle 100 is aligned with sensor
housing grommet 251 and ready for insertion into the subcutaneous
tissue of a patient. Also, cam surface 211 of inserter housing 202
is more clearly shown with first and second catch surfaces 210,
210', respectively.
[0166] FIG. 20 is a top view of inserter housing assembly 222 with
a view line 21-21 taken longitudinally through cam surface 211. It
should be noted that in this embodiment, there are four cam
surfaces 211 where each one of the cam surfaces 211 interacts with
one of four resilient locking catches of deployment button 204 but
that fewer or greater number of resilient locking catches may
optionally be preferred.
[0167] FIG. 21 is a cross-sectional view of inserter housing
assembly 222 taken along view line 21-21 in FIG. 20. This
cross-sectional view shows the contour of cam surface 211 with
resilient locking catch 214 holding deployment button 204 in a
ready-to-use position while preventing separation of deployment
button 204 from inserter housing 202 post assembly. FIG. 22 is an
enlarged view of the corresponding area outlined by reference
ellipse 22 in FIG. 21. As seen in FIG. 22, resilient locking catch
214 is captured by first catch surface 210, which prevents
deployment button 204 from being easily and inadvertently separated
from inserter housing 202 once assembled to inserter housing 202.
In this embodiment, a recess 118b formed into an inside surface
118a of housing wall 118 creates first catch surface 210 where
first catch surface 210 is transverse to inside surface 118a such
that when deployment button 204 is assembled within (i.e. inserted
into) inserter housing 202, resilient locking catch 214 is biased
inwardly by housing wall 118 until deployment button 204 reaches a
predefined location defined by recess 118b and first catch surface
210. When resilient locking catch 214 reaches recess 118b of first
catch surface 210, locking catch 214 is forced into recess 118b and
butts up against first catch surface 210, which is caused by the
imparted bias of the resilient locking catch 214 moving to a more
relaxed state. Recess 118b also has a sloping recess surface 118c
that extends back towards inside surface 118a and away from first
catch surface 210. Sloping recess surface 118c resists deployment
of deployment button 204, which requires an initial applied force
of greater than 1.5 lbs. followed by an applied force of less than
1.5 lbs. The initial applied force, also called the actuation
force, is an applied force of less than 2.5 lbs. (1.13 kg) but
greater than 1 lb. (453.6 g), which is discussed below. The
combination of cam surface 211, cam surface portion 211a, recess
118b, sloping recess surface 118c, first and second catch surfaces
210, 210', and resilient locking catch form a cam follower
deployment structure 209.
[0168] Along cam surface 211, housing wall 118 decreases in
thickness from or adjacent to inside surface 118a at a location
adjacent first catch surface 210 as indicated by arrows A along a
predefined distance L to a second location as indicated by arrows B
adjacent second catch surface 210'. As shown in FIG. 22, cam
surface 211 changes direction and a cam surface portion 211a slopes
towards inside surface 118a of housing wall 118 for a short
distance to second catch surface 210'. The distance between first
and second catch surfaces 210, 210' for this embodiment is about
0.44 inches (about 11.1 to 11.2 mm). Cam surface portion 211a
causes a small increase in deployment force caused by cam surface
portion 211a forcing resilient locking catch 214 back towards a
more biased orientation before releasing into second catch surface
210'
[0169] The cam follower deployment structure 209 was deliberately
designed to provide the patient a tactile feel during deployment as
well as to build momentum during actuation. The profile of cam
follower deployment structure 209 determines the initial deployment
force required for actuation. The insertion force of the needle was
previously discussed in relation to FIGS. 1, 2 and 6. However,
needle insertion force is not the only factor that determines the
successful deployment of a subcutaneous sensor. The design of the
insertion mechanism, the actuation force and the needle insertion
force combine to determine the comfort or discomfort experienced by
the patient. It is important to note that for continuous glucose
monitoring (CGM) systems, it is the patient who typically
self-administers by performing the insertion and deployment of the
needle and glucose sensor into the patient's own subcutaneous
tissue. This is akin to self-mutilation since pain is typically
associated with a needle piercing the skin. Inflicting pain on
oneself is not a natural state of being. For most patients, this is
difficult to do to oneself. All of the brands disclosed in FIGS. 1,
2 and 6 either use comparatively larger needles and/or use an
insertion mechanism that could cause a patient to not follow
through completely during the insertion process of the needle and
subcutaneous sensor before the subcutaneous sensor is fully
implanted and released from the insertion needle. Cam surface 211
and the cam follower (i.e. resilient locking catch 214) provides a
quick and easy mechanism that completes the sensor deployment
process and removal of the deployment mechanism from the inserted
subcutaneous sensor once the patient actuates the deployment
mechanism such that the patient has no control over the insertion
action once activated with respect to insertion of the subcutaneous
sensor because of the applied force profile during use of the
inserter assembly 200. In other words, the patient is unable to
consciously or subconsciously not follow through to completing the
sensor implantation process by lessening the insertion/applied
force on the inserter assembly.
[0170] Relationship of Actuation Force, Needle Insertion Force and
Inserter Assembly
[0171] The relationship of actuation force, needle insertion force
and the inserter assembly with cam surface 211 and cam
follower/resilient locking catch 214 is explored using a Mecmesin
2.5xt Force Tester. Five samples were deployed using the Mecmesin
2.5xt Force Tester as the method of actuation. The specific test
setup included a 50N load cell, a sample frequency of 100 Hz,
displacement of 0.44 inches, a speed of 10 inches per minute,
synthetic skin such as, for example, SIP-10 by SIMUlab, and
inserter assembly 200 of the present invention. The Mecmesin Force
Tester was set up to push deployment button 204 on inserter
assembly 200. The load cell measures a compressive force, which is
the reaction force imposed by the cam mechanism (i.e. cam surface
211 and resilient locking catch 214) as well as the needle
penetration of the synthetic skin sample. The Mecmesin will
capture/record the peak force, the average force and calculate the
work/energy under the generated curve for each sample.
[0172] Table 1 shows the data recorded by the Mecmesin 2.5xt Force
Tester of the deployment force with needle. As previously
described, the peak force, work and average force was recorded for
each of the five inserter assemblies 200.
TABLE-US-00001 TABLE 1 Deployment Force with Needle Sample Peak
Force (lbf) Work (lbf. in) Average Force (lbf) 1 2.1648 0.303758
0.6784 2 2.2086 0.361481 0.7623 3 2.2674 0.415904 0.8861 4 1.9226
0.361209 0.7674 5 2.0959 0.307079 0.6776 MEAN 2.1319 0.349886
0.7543 SD 0.133 0.0463 0.0855 MIN 1.9226 0.303758 0.6776 MAX 2.2674
0.415904 0.8861
[0173] Turning now to FIGS. 23-28, there is shown graphical
illustrations of the force versus distance of inserter mechanism
200. FIG. 23 is a graph showing the force versus distance data for
all five inserter mechanisms 200 used in the testing. As seen in
FIG. 23, the deployment force required to cause deployment button
204 to release from first catch surface 210 and begin the slide
along cam surface 211. As confirmed by the peak force data in Table
1 and the graphical illustration in FIG. 23, the actuation force to
begin the actuation process is between 1.5 lbs. (680.4 g) and 2.5
lbs. (1.13 kg). The sharp drop in the amount of force down to about
0.5 lbs. (226.8 g) or less is a result of cam surface 211 having
the sloping structure previously described. The peak force
variation is due to the variation in the test fixture setup as well
as reusing inserter components that are designed for one time use.
Notwithstanding these variations, the standard deviation in the
peak actuation force was only 0.133 lbf. (lbf meaning pounds of
force). It should be noted that the time of the test can be
calculated from the speed of the Mecmesin Force Tester. The
distance is about 0.44 inches and the speed of the Force Tester is
10 inches per minute. The time to conduct the test is about 2.6
seconds. In use, however, the actual time lapsed between actuation,
implantation of sensor 100 into the subcutaneous tissue and removal
of a post-actuation inserter assembly 201' from the sensor housing
206 is considerably shorter. Post-actuation inserter assembly 201'
contains deployment button 204, inserter housing 202, and needle
assembly 208 while the sensor housing 206 remains on the patient's
skin. The time period from actuation of the inserter assembly 202
to release of the post-actuation inserter assembly 201' is less
than one second, and less than 0.5 seconds. It is typically in the
range of less than 0.25 seconds to 0.8 seconds, or in the range of
0.25 seconds to 0.5 seconds, or in the range of 0.5 seconds to 0.8
seconds.
[0174] Turning now to FIGS. 24 to 28, there is shown in each figure
a graphical illustration of the data for a single sample. As
disclosed previously, the typical insertion depth of the sensor
into the subcutaneous tissue during use is from 4 mm to 7 mm
(.+-.0.3 mm) for measurement of subcutaneous glucose but a range of
2 mm to 10 mm is also acceptable. This means that the sharp/needle
must penetrate the subcutaneous tissue to a depth greater than the
sensor insertion depth since the sensor is carried within the
slotted needle 100 during sensor insertion. On average as the
needle penetrates the synthetic skin sample, the force remains at a
relatively low level (between 0.5 and 1 lbf) and begins to rise as
the needle penetrates beyond 0.2 inches until furthest penetration
is achieved (the applied force increases to less than 1.5 lbf). The
small bump at approximately 0.4 inch distance represents the
increase in force needed for the cam follower (i.e. resilient
locking catch 214) to get past cam surface portion 211a and into
second catch surface 210'. However as shown in each figure, the
momentum that is built up by the sudden drop in force after the
initial applied force of about 2 lbs. is reached (which is caused
by the design of the cam follower deployment structure 209)
minimizes any effect of the small rise in needle insertion force
that occurs until furthest depth penetration is reached and needle
100 is released. Compare this to the constant rise in applied force
shown in FIGS. 3 and 6.
[0175] An important feature of cam surface 211 is that, once the
initial applied force is reached, the force to maintain deployment
of button 204 greatly reduces, and the device is fully deployed
before the patient can abort deployment such that partial
deployment is not possible. This important safety feature ensures
that a partially deployed system cannot happen and greatly
simplifies the FMEA analysis (failure mode and effects analysis) as
well as reduces the hazard and risk of the overall system. The
hazard and risk includes, but are not limited to, re-deployment of
the needle and sensor into the same insertion point, fouling of the
sensor caused by blood forming in the subcutaneous wound as a
result of partial deployment, damage to the sensor as a result of
partial deployment, etc.
[0176] One of the advantages of using such a cam surface 211 with
recess 118b and sloping recess surface 118c is that a deployment
button spring is not needed to maintain deployment button in the
ready-to-use position. Another advantage over the use of a
deployment button spring is that the deployment button spring
increases resistance against the downward movement of the
deployment button due to the deployment button spring undergoing
compression, which may cause improper insertion and/or partial
insertion and then removal when the force used to depress
deployment button 204 is inadequate or stopped short of the
deployment button's end point. Another drawback is that such a
failure allows re-deployment of deployment button 204 after a first
attempted insertion. The cam surface 211, on the other hand, has
the advantage of no spring biasing resistance increasing as
deployment button 204 moves against the spring and the advantage of
lessened resistance between resilient locking catch 214 of
deployment button 204 and inserter housing wall 218 as deployment
button 204 is depressed due to the decreasing wall thickness of
housing wall 218 along cam surface 211 allowing relaxation of the
biasing force imparted into locking catch 214. This ensures that
deployment button 204 is pushed completely to the predefined depth
where resilient locking catch 214 engages second catch surface
210'.
[0177] FIG. 29 is a cross-sectional side view of the inserter
assembly 200 of FIG. 19 in a fully-inserted position. At this point
during the insertion process, needle 100 and sensor 500 penetrate
the subcutaneous tissue 1. Deployment button 204 contacts one or
more inserter housing stop surfaces 203. A portion of housing stop
surfaces 203 also interact with needle carrier catch 235 by pushing
needle carrier catch 235 inwardly toward needle 100 and releasing
needle carrier catch 235 away from button catch surface 240.
[0178] FIG. 30 is a top view of inserter housing assembly 222 with
a view line 25-25 taken longitudinally through cam surface 211.
FIG. 31 is a cross-sectional view of inserter housing assembly 222
taken along view line 32-32 in FIG. 30. This cross-sectional view
shows the contour of cam surface 211 with resilient locking catch
214 holding deployment button 204 in an inserted position. FIG. 32
is an enlarged view of the corresponding area outlined by reference
ellipse 26 in FIG. 31.
[0179] As seen in FIG. 32, resilient locking catch 214 is now
captured by second catch surface 210', which prevents re-use and
re-deployment of deployment button 204. When resilient locking
catch 214 reaches the recess of second catch surface 210', locking
catch 214 is forced to align with first catch surface 210'.
[0180] Turning now to FIGS. 33-36, the action of inserter assembly
200 will be explained. Once deployment button 204 is pressed and
needle 100 and sensor 500 are inserted into the subcutaneous
tissue, FIG. 33 shows that when deployment button 204 contacts one
or more inserter housing stop surfaces 203 and carrier catch 235 is
released from needle carrier catch 235, deployment spring 232 is no
longer confined to its compression state thereby allowing
deployment spring 232 to expand causing needle carrier 234 with
needle 100 to retract from the subcutaneous tissue and recede up
into deployment mechanism cavity 228. Substantially simultaneously
with the release of carrier catch 235, deployment button catch 214
slides into second catch surface 210' locking deployment button 204
in the inserted position.
[0181] It is noted that the term "substantially simultaneously"
means that the actions disclosed during sensor insertion into the
subcutaneous tissue are happening so quickly and close together in
time that the different actions are not perceived by the human
senses to occur other with a single action or a plurality of
simultaneous events.
[0182] While the above actions are occurring, sensor deployment
assembly 236 is substantially simultaneously being released from
sensor deployment assembly catch 214'. FIG. 34 is a cross-sectional
view of the inserter assembly 200 through sensor deployment
assembly catch 214'. As deployment button 204 bottoms out at
inserter housing stop surfaces 203, sensor deployment assembly
catch 214' interacts with sensor assembly catch release surface
206' forcing assembly catch 214' away from sensor deployment
assembly 236.
[0183] FIG. 35 shows the substantially simultaneous capture of
sensor deployment assembly 236 within sensor housing 206. Lower
deployment body 270 and upper deployment body 236a have at least
one aligned through opening 236b. Through opening 236b has a
through opening portion 236c in upper deployment body 236 and a
through opening portion 270a in lower deployment body 270 such that
a deployment body catch surface 270b is formed within through
opening 236b. Sensor housing 206 has at least one sensor deployment
assembly catch 206a that extends from an inside bottom surface 206b
and is positioned to align with through opening 236b. Sensor
deployment assembly catch 206a captures and retains sensor
deployment assembly 236 within sensor housing 206 substantially
simultaneously with the release of assembly catch 214'.
[0184] While all the previously disclosed capture and release
actions are occurring, FIG. 36 shows the substantially simultaneous
release of sensor housing 206 from inserter assembly 200. As
deployment button 204 is bottoming out, second button end 204b is
engaging housing locking mechanism 205. Prior to this release
action, recall that housing locking mechanism 205 has locking
mechanism end catch 205a that is hooked onto sensor housing catch
surface 206a and retains sensor housing 206 against second housing
end 215 of inserter housing 202. Second button end 204b
pushes/biases housing locking mechanism away from sensor housing
catch surface 206a releasing the inserter housing 202 from sensor
housing 206.
[0185] Through the substantially simultaneous catch and release
actions of inserter assembly 200, a needle 100 implants sensor 500
subcutaneously, retracts out of the subcutaneous tissue into
deployment button 204, sensor deployment assembly 236 is released
from deployment button 204 and captured within sensor housing 206,
and inserter housing 202 with deployment button 204 is released
from sensor housing 206 leaving sensor housing 206 with sensor 500
deployed subcutaneously.
[0186] FIG. 37 illustrates an enlarged view of sensor housing 206
with sensor deployment assembly 236 captured within sensor housing
206. For clarity, the subcutaneous tissue is not shown. Sensor
deployment assembly has a plurality of resilient electrical
coupling members 237. Electrical coupling members 237a-d couple to
the various electrodes of sensor 500. Electrical coupling members
237e-f is a continuity switch that completes the electrical circuit
between a battery 706 and module circuit board 702 in the sensor
housing cover assembly 850. FIG. 38 is a cross-sectional view of
the sensor housing of FIG. 37 with distal portion 502 of sensor 120
extending through sensor housing grommet 251 and a proximal portion
501 of sensor 120 captured between lower deployment body 270 and
upper deployment body 236a.
[0187] FIG. 39 is an enlarged, bottom, perspective view of one
embodiment of sensor housing cover assembly 850. As shown, cover
assembly 850 contains electronic module 700. Electronic module 700
includes module circuit board 702 and battery 706. Module circuit
board 702 has a plurality of electrical connectors 708 that
electrically couple the measurement circuit to the respective
electrical coupling members 237a-f of sensor deployment assembly
236. Sensor housing cover 850 captures assembly gasket 802 between
the perimeter of cover 850 and the perimeter 206'' of sensor
housing 206 by the interlocking of resilient cover locking tab 854
with sensor housing catch surface 206a. In this embodiment, there
are two cover locking tabs 854, one on each side of cover 850. In
other embodiments, cover 850 may have only one releasable locking
tab 854 while the opposite side has only a fixed locking tab that
engages a housing catch surface by way of a hinge type action where
the fixed locking tab is hooked to the housing catch surface first
followed by the releasable locking tab 854 engaging sensor housing
catch surface 206a.
[0188] FIG. 40 show sensor housing cover 850 mated to sensor
housing 206. FIG. 41 is a cross-sectional view of sensor housing
cover 850 and sensor housing 206 in FIG. 40 showing battery 706 and
electronic module 700 and their location relative to their position
with sensor housing 206 and sensor deployment assembly 236.
[0189] There are several advantages of the various embodiments of
the present invention. One aspect of the present invention provides
an advantage for a nearly pain-free insertion of the sensor
subcutaneously into the skin of a patient. Another aspect of the
present invention provides the advantage of a single action that
implants the sensor 120, retracts the needle/sharp 100, and
releases the inserter assembly 200 leaving the sensor housing 206
with the sensor 120 implanted where the sensor housing is ready for
receiving the electronic module 700. In yet another aspect of the
present invention, another advantage is the inserter assembly
design incorporates a further useful feature, which is the safe
retraction of the sharp for safe disposal. A sharp is defined by
the FDA (the US Food and Drug Administration) as a device with
sharp edges that can puncture or cut skin, and includes devices
such as needles, syringes, infusion sets and lancets. Improper
disposal or handling of sharps can cause accidental needle stick
injuries including transmission of Hepatitis B (HBV), Hepatitis C
(HBC) and Human Immunodeficiency Virus (HIV). Used sharps must be
placed in a "sharps" container such as the BD.TM. Home Sharps
Container, and fully sealed, before checking with local laws on
proper disposal. As previously disclosed, the structural feature of
cam surface 211 along with first and second catch surfaces 210,
210' prevents partial deployment of button 204 and the risk that
partial deployment creates.
[0190] FIGS. 9, 19 and 33 show the sharp fully enclosed within
inserter assembly 200. The sharp is fully covered and is not
accessible by finger. By design, the device cannot be made to
re-deploy the sharp. No special "sharps" container is required to
store and dispose of the inserter housing after sensor deployment.
The entire body can be disposed of according to local laws.
[0191] Sensor Construction:
[0192] Construction of the novel, multi-layer sensor substrate 500
will not be described. FIG. 42 shows a perspective illustration of
one embodiment of a multi-layer sensor assembly 500 ready for
deposition of reagents to create a continuous monitoring sensor 120
having, in this embodiment, a reference electrode 134, a blank or
second working electrode 133, a counter electrode 132, and a first
working electrode 130. Electrodes 130, 132, 133, 134 are formed at
a substrate distal end portion 502 and communicate electrically
through assembly middle portion 530 with electrically-conductive
contact pads 503 at a substrate proximal end portion 501.
Multi-layer sensor substrate 500 is useful to form a subcutaneous
analyte sensor, such as a glucose monitoring sensor.
[0193] A sensing layer (not shown) is formed over each of the first
and second working electrodes 130, 133. The sensing layer is made
up of three coating layers, a base coating layer, a second coating
layer and a third or top coating layer. The base coating layer
contains poly-2-hydroxyethyl methacrylate (PHEMA) and is the
coating that is disposed directly on the exposed metal at the
bottom of the respective wells at substrate distal end portion 502.
Specific to the first working electrode where glucose is measured,
glucose oxidase and/or glucose dehydrogenase is also included. The
second working or blank electrode does not contain any enzyme and
is used only for measuring background noise and/or interferents in
the sample since the first working electrode will have a total
current that include a portion driven by the amount of glucose in
the subcutaneous tissue as well as the background noise and/or
interferents derived current. Using an algorithm to subtract the
current derived from the second working or blank electrode from the
first working electrode provides a more accurate glucose
measurement. The second coating layer is disposed directly on the
base coating layer and contains PHEMA and a plurality of
microspheres from polydimethylsiloxane (PDMS). PDMS is a material a
material having substantially no or little permeability to glucose
but a substantially high permeability to oxygen. The third or top
coating layer is disposed directly on the second coating layer and
contains PHEMA and catalase. Catalase is a material that prevents
release of hydrogen peroxide from the sensing layer into the
surrounding environment. In this case, the surrounding subcutaneous
tissue.
[0194] For the reference electrode 134, a silver-silver chloride
(AgCl) layer is created on the metal at the bottom of the well and
then the AgCl layer is covered with a hydrogel membrane. The
counter electrode 132 has the metal at the bottom of the well
covered only with a hydrogel membrane.
[0195] Referring now to FIG. 43, a perspective, exploded
illustration shows a base layer 510, a middle layer 550, and a top
layer 580 that together comprise multi-layer sensor substrate 500.
"Middle layer" herein means the layer adjacent to the top layer 580
without any intervening, electrically-insulating layer when there
are other layers between base layer 510 and middle layer 550. Base
layer 510 is electrically insulating and includes a base proximal
end portion 514, a base distal end portion 516, and a base middle
portion 518 between base proximal end portion 514 and base distal
end portion 516. A base metallized layer 520 is disposed on base
layer 510 and defines at least one circuit 522 extending
longitudinally along base layer 510. Each circuit 522 has an
electrically-conductive contact pad 524 formed at base proximal end
portion and an electrically-conductive contact pad 526 formed at
base distal end portion 516 with an electrically-conductive trace
528 electrically coupling electrically-conductive contact pad 524
at the base proximal end 514 with electrically-conductive pad 526
at base distal end 516.
[0196] Middle layer 550, also electrically insulating, is disposed
over base layer 510 and includes a middle layer proximal end
portion 554, a middle layer distal end portion 556, and a middle
layer middle portion 558. Middle layer 550 has a size and shape
corresponding to base layer 510 and that is aligned with base layer
510. Middle layer 550 includes electrically-conductive contact pads
562 at middle layer distal end portion 556 adapted to receive an
electrode material or reagent to form a respective electrode. Each
electrically-conductive contact pad 560 at middle layer proximal
end portion 554 is adapted to receive an electrical contact.
[0197] The top layer 580, also electrically-insulating, is disposed
over middle layer 550. Top layer 580 has a size and shape
corresponding to middle layer 550 and base layer 510. Top layer 580
has a top layer proximal end portion 582, a top layer distal end
portion 584, and a top layer middle portion 586, where top layer
580 aligned with base layer 510 and middle layer 550. Top layer 580
has a plurality of openings that include contact openings 590 on
substrate proximal end portion 501 (See FIG. 42) and sensor wells
592 on substrate distal end portion 502 (see FIG. 42). Contact
openings 590 and sensor wells 592 coincide with
electrically-conductive contact pads 560, 562, respectively, of
middle layer 550. Base layer 510, middle layer 550, and top layer
580 are manufactured with circuits 552, 572 on base layer 510 and
middle layer 550, respectively, to create multi-layer sensor
substrate 500 with substrate proximal end portion 501, substrate
distal end portion 502, and assembly middle portion 503 extending
longitudinally between substrate proximal end portion 501 and
substrate distal end portion 502 as shown, for example, in FIG. 42.
Substrate distal end portion 502 and assembly middle portion 503
each have a width of about 279 microns.
[0198] Referring now to FIGS. 44-46, base layer 510 is shown in a
plan view in FIG. 44, base proximal end portion 514 is shown
enlarged in FIG. 45, and base distal end portion 516 is shown
enlarged in FIG. 46. Base layer 510 has a base layer substrate 512
that is electrically insulating and includes a base proximal end
portion 514, a base distal end portion 516, and a base middle
portion 518 extending between and connecting base proximal end
portion 514 and base distal end portion 516. In one embodiment,
base layer substrate 512 is made of polyimide and has a thickness
from 7.5 .mu.m to 12.5 .mu.m. For example, base layer substrate 512
has a thickness of about 10 .mu.m. In one embodiment discussed in
more detail below, base layer substrate 512 may be formed by spin
coating polyimide on a glass plate followed by further lithographic
processing.
[0199] Base metallized layer 520 is disposed directly onto base
layer substrate 512 and defines at least one circuit extending
longitudinally along base layer substrate 512 from base layer
proximal end portion 514 to base layer distal end portion 516. In
one embodiment as shown, base metallized layer 520 defines two
circuits 522, where each circuit 522a, 522b has an
electrically-conductive contact pad 524a, 524b, respectively,
formed at base proximal end portion 514. Circuit 522a has
electrically-conductive contact pads 526a1-526a2, formed at base
distal end portion 516. Circuit 522b has electrically-conductive
contact pad 526b at distal end portion 516. Each circuit 522a, 522b
has an electrically-conductive trace 528a, 528b electrically
coupling electrically-conductive contact pads 524a, 524b at the
base proximal end portion 514 with the respective
electrically-conductive pads 526a1-526a2 and 526b at the base
distal end portion 516. For example, circuit 522a is configured for
a working electrode 130 of sensor assembly 120 and circuit 522b is
configured for a blank electrode 133 of sensor assembly 120 (shown
in FIG. 42).
[0200] Comparing distal end portions 516 and 556 of FIGS. 46 and
49, respectively, contact pads 526a1-526a2 of metallized layer 520
each have a size and shape corresponding to one or more contact
pads 562 of middle metallized layer 550, rather than being sized
only for through openings 564 of middle layer substrate 552. An
advantage of this configuration is that contact pads 526a1-526a2
reduce stress induced to contact pads 562 caused by the spin
coating process described below, which stress leads to cracking of
contact pads 562 in middle metallized layer 570. In one embodiment,
for example, contact pad 526a1 is sized and shaped to substantially
underlie contact pad 562a of middle metallized layer 570, but not
through opening 564c. Contact pad 526a2 is sized and shaped to
substantially underlie contact pads 562b, 562c and through opening
564d of middle metallized layer 570.
[0201] In one embodiment, base metallized layer 520 has an overall
thickness of 1200.+-.300 .ANG.. For example, base metallized layer
520 is formed by depositing a first part of chromium (200.+-.150
.ANG.) directly onto and against base layer substrate 512, a second
part of gold (1000.+-.150 .ANG.) disposed directly onto the
chromium, and a third part of chromium (200.+-.150 .ANG.) disposed
directly onto the gold. In other words, the base metallized layer
520 has a thickness in the range of about 900 Angstroms to about
1,500 Angstroms. Other conductive materials and thicknesses are
acceptable for base metallized layer 520 depending on the intended
use of sensor assembly 120.
[0202] Referring now to FIGS. 47-49, middle layer 550 is shown in a
plan view in FIG. 47, second proximal end portion 554 is shown
enlarged in FIG. 48, and second distal end portion 556 is shown
enlarged in FIG. 49. Middle layer 550 has a middle layer substrate
552 that is electrically insulating and defines a plurality of
middle layer through openings 564 with side walls extending to base
layer 510, where each middle layer through opening 564 communicates
electrically with a respective electrically-conductive contact pad
524, 526 of circuit 522 of base layer 510. In one embodiment,
middle layer substrate 552 is made of polyimide that is spin coated
onto base layer 510 and base metallized layer 520 as discussed
below, for example, in a method 600 of making multi-layer sensor
substrate 500. In one embodiment, middle layer substrate 552 has a
thickness from 7.5 .mu.m to 12.5 .mu.m, such as about 10 .mu.m.
[0203] A middle metallized layer 570 is disposed directly onto
middle layer substrate 552 and the side walls of through openings
564 to define at least two middle layer circuits 572, where each
middle layer circuit 572 has electrically-conductive contact pad
560 formed at middle layer proximal end portion 554 and
electrically-conductive contact pad 562 formed at middle layer
distal end portion 556 with an electrically-conductive trace 574
electrically coupling contact pad 560 at middle layer proximal end
portion 554 with electrically-conductive contact pad 562 at middle
layer distal end portion 556, and a least one or more additional
electrically conductive pads 560, 562 in electrical contact with
through openings 564. The at least one or more additional
electrically conductive pads 560, 562 electrically coupled to base
layer circuit(s) 522 by way of through openings or vias 564. For
example, middle metallized layer 570 is deposited on top surface
550a, on the sidewalls of through openings 564, and onto part of
base metallized layer 520 creating electrical continuity between
the base metallized layer 520 and the respective contact pads 560,
562.
[0204] In one embodiment of middle layer proximal end portion 554
as shown in FIG. 48, for example, middle layer circuit 572a
includes contact pad 560b and middle layer circuit 572b includes
contact pad 560c. Contact pads 560a, 560d are isolated from middle
layer circuits 572a, 572b. Contact pad 560a (which is electrically
coupled to working electrode 130 at the middle layer distal end
556) defines two through openings 564a and contact pad 560d (e.g.,
for blank electrode 133) defines two through openings 564b, each of
which has electrical continuity to base metallized layer 520 at
contact pad 524a and contact pad 524b, respectively (shown in FIG.
45).
[0205] In one embodiment of middle layer distal end portion 556 as
shown in FIG. 49, for example, middle layer circuit 572a includes
contact pad 562a and middle layer circuit 572b includes contact pad
562c. Contact pads 562b, 562d are isolated from middle layer
circuits 572a, 572b. Middle layer substrate 552 has through opening
564c at with contact pad 562b (e.g., for blank electrode 133)
having electrical continuity to base metallized layer 520 at
contact pad 526b (shown in FIG. 46). Middle layer substrate 552
defines through opening 564d with contact pad 562d having
electrical continuity with contact pad 526a2 (shown in FIG. 46).
Contact pads 562d and 562b are isolated from middle layer circuits
572a, 572b. Contact pad 562a (i.e. the reference electrode 134) is
segmented into 3 contact pad portions 562a1, 562a2 and 562a3. The
reference electrode 134 is segmented to prevent cracking of the
Ag/AgCl and delamination from contact pad 562a, which is a definite
advantage where sensor 500 is implanted subcutaneously in a
patient.
[0206] Referring now to FIG. 50, a cross-sectional slice of
multi-layer sensor substrate 500 taken through substrate proximal
end portion 501 at contact pad 524a is used to show the electrical
continuity between base layer 510 and middle layer 550. Contact pad
524a is on base layer substrate 512, middle layer substrate 552 is
disposed on base layer 510, contact pad 564a is disposed on middle
layer substrate 552, and top layer 580 is disposed on middle layer
550. Contact pad 560a is disposed on middle layer substrate 552,
including sidewalls 564a' of through openings 564a in middle layer
substrate 552, thereby allowing electrical continuity between
contact pad 560a and contact pad 524a. Top layer 580 is
electrically insulating and is disposed on middle layer 550 to
isolate middle layer 550 from the surrounding environment. In one
embodiment, top layer 580 is polyimide that is spin coated onto
middle layer 550 and has a thickness of about 55 .mu.m after
curing. An advantage of this multilayer construction method with
connected vias is the overall width of multi-layer sensor assembly
500 is maintained as small as possible while allowing the creation
of multiple electrodes with their accompanying
electrically-conductive traces.
[0207] In one embodiment, base metallized layer 520 and middle
metallized layer 570 each includes gold. In another embodiment,
base metallized layer 520 and middle metallized layer 570 each
includes a layer of chromium disposed directly on base layer
substrate 512 and middle layer substrate 552, respectively, and a
layer of gold disposed directly on top of the layer of chromium. In
another embodiment, middle metallized layer 570 includes a layer of
chromium disposed directly on the middle layer substrate 552, a
layer of gold disposed directly on top of the layer of chromium,
and a layer of platinum disposed directly on top of the layer of
gold.
[0208] Referring now to FIG. 51, a side elevational view shows
multi-layer sensor substrate 500 with proximal end portion 501 and
distal end portion 502. The process used in making multi-layer
sensor substrate 500 caused the completed sensor 120 to have an
arcuate shape along is length. The arcuate shape forms a bend
radius R to top surface 122. In one embodiment, bend radius R is no
greater than 1.375 inch (35 mm). The bend radius R is a planned
feature of the present invention. An advantage of the bend radius R
is that the sensor distal end portion 502 of continuous monitoring
sensor 120 is retained and firmly nested in the cannula/needle 100
during deployment into the patient due to frictional forces of
multi-layer sensor substrate 500 engaging the cannula/needle inside
wall without any other component or structure to ensure the sensor
120 remains intact and useable through the insertion process in the
subcutaneous tissue. This is especially important considering the
size of the distal end portion 502 of sensor 120 being 0.011 inches
wide (279 microns) and 0.003 inches thick (75 microns).
[0209] FIG. 52 shows one embodiment of system 1000 in use after
insertion of sensor 120 into the subcutaneous tissue. As shown,
FIG. 52 shows examples of electronic device 902, 902', a
transmitter 1004 (which is sensor housing 206 containing sensor
deployment assembly 236 and sensor housing cover 850) on the
patient's arm, where transmitter 1004 communicates analyte
measurement data from continuous monitoring sensor 120 deployed
into the patient to electronic device 902, where the data is
displayed to the user on a user interface 918.
[0210] System 1000 includes inserter assembly 200, a transmitter
1004, system software installed on an electronic device 902
equipped for wireless communication with transmitter 1004.
Optionally, system 1000 utilizes an analyte strip reader 906 for
calibration. Examples of electronic device 902 include a computer,
a tablet computer, a phone, a data logger, a watch, an automobile
information/entertainment system, or other electronic device.
Wireless communication may be via radio frequency (RF)
communication, Wi-Fi, BlueTooth, near-field communication (NFC), a
sensor radio, mobile body area networks (MBAN) or other wireless
communication protocol. In this embodiment, strip reader 906 has
integrated BLE (BlueTooth low energy) and will send calibration
data wirelessly to electronic device 902 and query the patient
regarding the patient's intention to use the new calibration data
point.
[0211] As discussed previously, the inserter assembly 200 is used
to deploy continuous monitoring sensor 120 into the subject after
positioning the inserter assembly 200 on the subject's body,
deploying continuous monitoring sensor 120, and attaching the
sensor housing cover 850 containing electronic module 700 and
battery 706 (which includes transmitter 804) onto sensor housing
206 thereby forming transmitter 1004.
[0212] In one embodiment, transmitter 1004 communicates to the
electronic device 902 using a wireless personal area network
(WPAN), such as Bluetooth Low Energy (BLE). In other embodiments,
other wireless communication protocols may be used with
communication generally effective within a range of a few
centimeters to a few meters. In some embodiments, for example, the
system software is configured to communicate with Android and/or
Apple software platforms installed on mobile phones and the like
and has a range of up to thirty feet (about 9.2 meters).
[0213] In one embodiment, transmitter 1004 is designed to conserve
power and operates via standard Bluetooth BLE protocol. For
example, sensor readings from continuous monitoring sensor 120 are
transmitted from transmitter 1004 every five minutes and the sensor
reading is promptly displayed to the user after being received by
the user's electronic device 902. Typically, transmitter 1004 will
successfully connect with the electronic device 902 after one or
two attempts.
[0214] In one embodiment, system 1000 uses universally unique
identifier (UUID) filtering to prevent unwanted communication from
another device. It is expected that multiple devices may be present
and discoverable in proximity to electronic device 902,
particularly when the user is in a densely populated area as in a
subway, concerts, or other public locations.
[0215] In one embodiment, system 1000 utilizes calibration data
obtained wirelessly from a separate strip reader. For example, a
finger strip reading for glucose is taken and then either manually
or automatically entered in system 1000 for calibration. In one
embodiment, the system 1000 software application has a means for
the user to manually enter a one-point calibration value taken from
any meter. For example, the user uses the interface of the
electronic device 902 to enter a calibration reading of 100 mg/dl
obtained using a separate strip reader. After entering the
calibration data, the user can accept, reject, or manually re-enter
the calibration data. In other embodiments, the system software
receives BLE calibration information from the external meter. After
system 1000 receives the calibration data, the user can accept,
reject, or manually re-enter this calibration data into the user
interface.
[0216] The system software provides a user interface 918, one
example of which is a touch-sensitive display screen. In one
embodiment, user interface 918 has a main screen 909 with
indicators 910a for radio strength and battery strength. Another
indicator 910b displays the analyte concentration (e.g., glucose
concentration) in units of mg/dL (milligrams per deciliter) or
mmol/L (millimoles per liter). Indicator 1010c displays a glucose
trending arrow to communicate to the user whether the analyte
concentration (e.g., glucose) is increasing, decreasing, or
unchanged. In one embodiment, indicator 910c for the trending arrow
also communicates the relative rate of change.
[0217] In one embodiment, for example, a rate of change having an
absolute value equal to or greater than a predefined value (e.g.,
.gtoreq.3 mg/dL) is displayed as two vertically-oriented arrows (up
or down); a rate of change in a second predefined range with an
absolute value less than the predefined value (e.g., 2-3 mg/dL is
displayed as a single vertically-oriented arrow (up or down); a
rate of change in a third predefined range with absolute value less
than the second predefined range (e.g., 1-2 mg/dL is displayed as
an arrow inclined at 45.degree. to the horizontal (up or down); and
a rate of change in a fourth predefined range with an absolute
value less than the absolute value of the third predefined range
(e.g., 1 mg/dL or less) is displayed as a horizontal arrow to
indicate a steady state. In one embodiment, the rate of change is
calculated based on five consecutive data points using the
following formula:
b = ( x - x _ ) .times. ( y - y _ ) ( - _ ) 2 ##EQU00001##
[0218] In one embodiment, analyte (e.g., glucose) concentration is
updated every five minutes with data from transmitter 1004 and
displayed on main screen 909. Optionally, transmitted data is
updated and stored in transmitter 1004 in case electronic device
902 is out of range or unable to receive during that period. In one
embodiment, each transmission by transmitter 1004 includes a
predefined number of previous data points (e.g., five) to fill in
missing data in the event electronic device 902 is unable to
receive during that period.
[0219] Main screen 909 also displays a plot 911 of analyte
concentration versus time. In one embodiment, the Y-axis (analyte
concentration) is configured to automatically scale with a minimum
Y-axis value 10% below the minimum value of plotted data and the
maximum Y-axis value 10% above the maximum value of plotted data.
The X axis may be configured to display a timeframe of the user's
choosing.
[0220] Main screen 909 also displays a macro timescale 912 of data
that includes data displayed in plot 911. Part of the data
displayed in macro timescale 912 is highlighted and corresponds to
the data displayed in plot 911. For example, macro timescale 912
may be configured to display analyte concentration data over three
hours, six hours, twelve hours, twenty-four hours, three days, or
one week. Accordingly, data displayed in plot 911 is a subset of
data displayed in macro timescale 912. In one embodiment,
highlighted area 913 of macro timescale 912 is an active element on
user interface 908. For example, by touching highlighted area 913
in the center and dragging left or right, the data of plot 911 is
selected and moved. Similarly, by touching highlighted area 913 on
left edge 913a or right edge 913b and dragging left or right,
highlighted area 913 is expanded or contracted along the time axis.
When the size or location of highlighted area 913 is adjusted, plot
911 is automatically updated to display data between the same
minimum time and maximum time of highlighted area 913. Main screen
909 also displays an active service icon 915. Selecting active
service icon 915 displays a service screen with indicators 910 for
calibration and customization. For example, the service screen
includes indicators 910 for setting upper and lower ranges, alarm
limits, displayed units, device pairing settings, time scale,
X-axis time domain, and the like. For example, the user accesses
the service screen to set the time range of data displayed in macro
timescale 912 and plot 911. Selecting the calibration icon opens a
calibration screen used to calibrate analyte data. In some
embodiments, the service screen includes instructions for use or a
link to access instructions for use.
[0221] For example, user-set or default values for maximum and
minimum concentration/control limits are displayed on plot 911 as
dashed lines 916a, 916b, respectively, extending horizontally. In
one embodiment, user-set control limits are not alarmed. Default
control limits provide upper and lower alert limits and upper and
lower reportable range limits. A reading above the maximum 916a or
below the minimum 916b results in an alarm, such as vibration or an
audible alert to the user. In one embodiment, maximum concentration
limit 916a has a default value of 510 mg/dL and minimum
concentration limit 916b has a default value of 90 mg/dL.
[0222] In some embodiments, system software is configured to
generate reports for health care professionals. For example,
touching an icon opens reports and configurations that could be
transferred to a Health Care Professional via the cloud, such as
the amount of time above and below target ranges; alarm reports,
CGM values; estimated A1C and eAG values, and analyte measurements
over time.
[0223] In one embodiment, system 1000 enables the user to manually
enter a one-point calibration value taken from a separate glucose
strip reader. For example, the user enters 100 mg/dl as obtained
from a test strip measurement. After entering calibration data, the
patient shall accept, reject, or manually re-enter this calibration
data into the user interface.
[0224] In another embodiment, system 1000 is configured to receive
calibration information from strip reader via BLE or other wireless
communication protocol.
[0225] In some embodiments, settings and preferences may be locked
and are accessed only by entering a password, biometric
information, or other information serving as a key to unlock the
settings and preferences menu.
[0226] In one embodiment, system 1000 performs general data
calculations using the following generic variable labels:
A0=(M*X+B)-(N*Y+C)
A1=A0+calibration adjustment
A2=A1/18.018018
X=((<channel 0>*0.000494)-1)*1000
Y=((<channel 1>*0.000494)-1)*1000
Generic variables are defined as follows:
[0227] A0 is uncalibrated CGM value in mg/dL
[0228] A1 is calibrated displayed CGM value in mg/dL
[0229] A2 is calibrated displayed CGM value in mmol/L (alternate
units)
[0230] X is the mV reading output of Channel 0 (the sensor signal
channel)
[0231] M is the slope correction factor Channel 0
[0232] B is offset correction factor for Channel 0
[0233] Y is the my reading output of Channel 1 (the blank signal
channel)
[0234] N is the slope correction factor for channel 1
[0235] C is the offset correction factor for channel 1
[0236] In one embodiment, values for M, B, N, and C variables are
stored on electronic device 902. In one embodiment, values A0, A1,
X, and Y are stored to a Sqlite Database along with date timestamp.
For example, datetime, channel-0-value, channel-1-value,
calculated-glucose value,
calculated-glucose-value-with-calibration, and device-id.
Optionally, a separate database includes patient-entered
calibration data with timestamp, such as datetime,
entered-calibration value, and device-id.
[0237] In one embodiment, values for A1 or A2 (values displayed to
the patient in plot 911) that are greater than a predefined maximum
limit (e.g., 800 mg/dL or 27.7 mmol/L) result in an error message
displayed on user interface 918, such as "Above Reportable Range."
Similarly, values for A1 or A2 of less than a predefined minimum
limit (e.g., 40 gm/dL or 2.2 mmol/L) result in an error message
displayed to the user, such as "Below Reportable Range."
[0238] Communication between transmitter 1004 and electronic device
902 is secure. For example, BLE-supported Security Manager Protocol
is utilized between transmitter 1004 and electronic device 902. SMP
defines the procedures and behavior to manage pairing,
authentication, and encryption between the devices, including
encryption and authentication, pairing and bonding, key generation
for device identity resolution, data signing, encryption, pairing
method based on the input/output capabilities of transmitter 1004
and electronic device 902.
[0239] In one embodiment, electronic device 902 is a watch
configured to communicate wirelessly with transmitter 1004. In such
an embodiment, system software includes three screens on the user
interface 918 of the electronic device 902' configured as a watch.
A first screen displays the most recent analyte concentration and
units of measurement. For example, glucose concentration is
displayed by indicator 910b in mg/dL or mmol/L and is updated every
five minutes. A trending arrow indicator 910c shows the relative
rate of change as discussed above.
[0240] A second screen displays the most recent glucose
concentration and units of measurement. Second screen displays plot
911 with analyte concentration data for the previous one hour,
where the Y-axis is glucose concentration and the X-axis is time.
Upper and lower limits 916a, 916b are displayed in dashed lines. A
third screen displays macro timescale 912 with twenty-four hours of
acquired data.
[0241] Subcutaneous Sensor Implantation Method:
[0242] Referring now to FIG. 53, a flow chart illustrates exemplary
steps of a method 1100 for continuous analyte measurement such as,
for example, glucose. To start, at step 1105 select an
pre-assembled inserter assembly 200 that contains sensor deployment
assembly 236 with a sensor 120. At step 1110, optionally place a
sensor housing adhesive pad 600 configured for use with sensor
housing 206 onto the bottom of the sensor housing if adhesive pad
is not pre-installed. It is contemplated that adhesive pad 600 may
already be attached to the inserter assembly 200 where the user
simply removes a backing for attaching the inserter assembly 200 to
a user's skin. It is further contemplated that other modes of
adhesively securing the sensor housing 206 to the patient may be
used, all as is well known in the art.
[0243] At step 1120, inserter assembly 200 is placed on the
insertion site of the patient with sensor housing 206 and, if
optionally attached, sensor housing adhesive pad 600 contacting the
patient's skin. In one embodiment, the area of contact is quite
small, measuring about 1 inch (25.4 mm) wide by about 1.5 inches
(38.1 mm) long. In one embodiment, step 1120 includes fixing
inserter assembly 200 to the skin using medical grade adhesive tape
or the like.
[0244] At step 1125, the user manually presses button 204 down to
its second position (down position) to drive the low-force
needle/sharp 100 and continuous monitoring sensor 120. Typically,
the needle/sharp 100 is inserted about 8 mm into the subcutaneous
tissue. Step 1125 has been shown to take about 0.1 lbs. of force
and be virtually painless to the patient.
[0245] At step 1130, deployment mechanism 208 "bottoms out" or
reaches its furthest downward position towards sensor housing 206.
An audible "click" along with a sensory vibration alerts the user.
At step 1135, the audible click and the sensory vibration indicates
to the user that the sensor 120 has been implanted, needle/sharp
100 has retracted back into inserter assembly 200, and inserter
assembly 200 has released from sensor housing 206.
[0246] During step 1135, deployment mechanism 208 automatically
retracts or moves from the pre-insertion needle carrier position
(down position) to a released carrier needle position (up
position), leaving continuous monitoring sensor 120 inserted about
7 mm into the skin. Needle/sharp 100 is released by the double
acting deployment mechanism 208 that quickly retracts needle/sharp
100 and needle carrier 234.
[0247] At step 1140, inserter housing 202, deployment button 204,
and deployment mechanism 208 (also collectively referred to as the
inserter assembly 200) are removed/displaced from sensor housing
206 without requiring any further action to be performed to cause
the inserter assembly 200 to release from the sensor housing 206.
As previously described, release of inserter assembly 200 from the
sensor housing 206 occurs automatically as deployment button 204
"bottoms out" and causes the release of locking mechanism 205
(e.g., pressing a snap feature) on inserter housing 202 away from
sensor housing 206. The sensor housing 206 containing the sensor
deployment assembly is left on the patient.
[0248] At step 1145, the sensor housing cover 850 containing the
electronic module 700 and battery 706 is installed onto the sensor
housing 206. Attaching sensor housing cover 850 onto sensor housing
206 automatically turns on power to electronic module 700 and the
install is complete at step 1150.
[0249] At step 1145, the completed sensor housing assembly is now
operational. The electronic module 700 begins receiving electrical
signals generated by sensor 120. The electrical signals generated
by sensor 120 that is implanted subcutaneously in a patient are
directly related to the analyte concentration in the subcutaneous
tissue. In the case of where a glucose sensor is used, the
electrical signals generated by sensor 120 are directly related to
the glucose concentration in the subcutaneous tissue. Electronic
module 700 contains the electronic and/or electrical components
that allows for measuring and recording the analyte of interest,
which in the case of continuous glucose monitoring, is glucose. The
data obtained from sensor 120 may be stored in electronic circuitry
of the electronic and/or electrical components in electronic module
700 for simultaneous or later displays and/or transmission of the
generated data. The electronic module may also include an inductive
charging capability so that the onboard battery source can be
conveniently charged without removal from the sensor housing.
[0250] Sensor Substrate Formation Method:
[0251] Referring now to FIG. 54, a flowchart illustrates steps in
one method 1200 of making multi-layer sensor substrate 500.
[0252] In step 1205, a piece of precision, flat soda-lime float
glass substrate is provided with a size of 4''.times.4'' and having
a tin coating on the back surface.
[0253] In step 1210, a border is metalized onto the glass front
side of the glass substrate. In one embodiment, the border has a
width of 4 mm. Metalizing the border is performed by first imaging
the border into a photoresist layer spin-coated onto the glass
substrate. Next, a layer of chromium is deposited on the
photoresist using a sputtering machine or thermal deposition. The
photoresist is lifted off using acetone, then the surface is
washed, baked dry, and plasma cleaned.
[0254] In step 1215, a first polyimide insulation layer (base layer
substrate 512) is applied and cured. In one embodiment, the first
polyimide layer is applied by spin coating and has a thickness of
10.0 .mu.m.+-.2.5 .mu.m after curing. For example, the polyimide is
applied by spin coating, followed by soft baking for ten minutes on
a hot plate at 100.degree. C. and curing in an oven or furnace by
ramping the temperature to 350.degree. C. and holding at
temperature for thirty minutes. After curing, the first polyimide
insulation layer thickness may be measured and verified.
[0255] In step 1220, base metallized layer 520 is applied to base
layer substrate 512 and processed. First, an RF etch at 580 W is
performed to clean the surface. In one embodiment, the base
metallized layer 520 is deposited by sputtering and is a three-part
metal layer that includes a first layer of chromium (thickness of
200.+-.150 .ANG.), a second layer of gold (1000.+-.150 .ANG.)
sputtered onto the chromium, and a third layer of chromium
(200.+-.150 .ANG.) sputtered onto the gold.
[0256] The base metallized layer 1220 is then imaged. First,
photoresist is spin-coated onto base metallized layer 520 and soft
baked on a hotplate as discussed above. Using a mask aligner, the
features are aligned and the photoresist is exposed using a first
metal layer mask. The photoresist is developed and plasma cleaned.
Next, exposed metal of base metallized layer 520 is removed using
ion milling, followed by removal of the remaining photoresist with
a solvent. Optionally, the resistance of the base layer substrate
512 is checked to ensure all metal was removed. Optionally,
conductive traces 528 of the base metallized layer 520 are
inspected for shorts and opens and corrected where possible. To
confirm operation of the circuit, measurements are taken for the
resistance between the "working" and "blank" traces 528 at various
locations. In one embodiment, the resistance is at least 10
M.OMEGA., which is the resistance of an open load.
[0257] In step 1225, middle layer substrate 552 (e.g., a second
polyimide insulative layer) is deposited onto the base layer 510
and processed. After depositing by spin coating, the middle layer
substrate 552 is soft-baked, and cured. In one embodiment, the
second polyimide insulation layer has a thickness of 10.0
.mu.m.+-.2.5 .mu.m after curing. The second polyimide insulative
layer is first soft baked for five minutes on a hot plate at
70.degree. C., then soft baked for ten minutes on a hot plate at
105.degree. C. Curing is performed in an oven or furnace by ramping
to 350.degree. C. and holding at temperature for thirty minutes,
followed by plasma cleaning. The middle layer substrate 552 is
imaged by applying photoresist, followed by alignment and exposing
the photoresist using a "via mask" on the mask aligner. The
photoresist is developed using a developer and rinsed in a spray
develop unit.
[0258] In step 1230, a middle metallized layer 570 is deposited on
the middle layer substrate 552 (second polyimide insulative layer)
and processed. Middle metallized layer may be deposited using a
sputtering machine or acceptable substitute. Optionally, this step
initially includes an RF etch at 580 W performed prior to metal
deposition for cleaning and preparing the surface. In one
embodiment, the middle metallized layer 570 is a four-part layer
that includes a first part of chromium (200.+-.150 .ANG.), a second
part of gold (1000.+-.150 .ANG.) deposited onto the chromium, a
third part of platinum (1000.+-.150 .ANG.) deposited onto the gold,
and a fourth part of chromium (200.+-.150 .ANG.) deposited onto the
platinum.
[0259] The middle metallized layer 570 is imaged. First,
photoresist is spin-coated onto the middle metallized layer 570
followed by soft baking on a hotplate. Next, the photoresist is
aligned and exposed using a second metal layer mask, followed by
development of the photoresist and plasma cleaning. Next, the
exposed metal of the middle metallized layer 570 is removed by ion
milling. The remaining photoresist is then removed. Optionally, a
resistance check is performed on the second polyimide insulative
layer (middle layer substrate 552) to ensure the excess metal of
the middle metallized layer 570 has been adequately removed.
Conductive traces 574 of middle layer 550 are inspected for shorts
and opens, followed by plasma cleaning.
[0260] Optionally, the resistance is checked for the middle
metallized layer 570. For example, the resistance is measured
between conductive traces 574. Preferably, the resistance is at
least 10 M.OMEGA. (Open Load).
[0261] In step 1235, top layer 580 (e.g., third polyimide
insulative layer) is applied to middle layer 550. In one
embodiment, top layer 580 is a biocompatible polyimide or an
acceptable substitute, where the polyimide is spin coated, soft
baked, and cured. Soft baking is performed for five minutes on a
hotplate at 70.degree. C., followed by soft baking for ten minutes
on a hotplate at 105.degree. C. In one embodiment, top layer 580
has a thickness of 55.0 .mu.m.+-.5.0 .mu.m after curing.
[0262] Top layer 580 is imaged to define contact openings 590 and
sensor wells 592 that extend through top layer 580 and correspond
to contact pads 560, 562, respectively, of middle metallized layer
570. In one embodiment, top layer 580 is polyimide with a thickness
of about 55 .mu.m after curing. After spin coating a layer of
photoresist, the top layer 580 is aligned and the photoresist is
exposed using a "well mask" on the mask aligner. The photoresist is
developed using a developer and rinsed in a spray develop unit.
Optionally, contact openings 590 and sensor wells 592 are inspected
for complete development and then spot checked for a pre-cure
height. The top layer 580 is then slow-cured in an oven or furnace
by ramping to 550.degree. C., holding at temperature for sixty
minutes, then ramping to 350.degree. C. and holding at temperature
for thirty minutes. After slowly cooling, the top layer 580 is
plasma cleaned and visually inspected using a microscope.
Optionally, the depth of contact openings 590 and sensor wells 592
may be checked at various locations.
[0263] In step 1240, the middle metallized layer is etched where it
is exposed through sensor wells 592 and contact openings 590 of the
top layer 580. For example, the fourth chrome layer of the middle
metallized layer 570 is chemically removed to expose the third
platinum layer on all sensor wells 592 and contact openings 590.
The sensor wells 592 and contact openings 590 are inspected for
complete chromium removal, followed by plasma cleaning of the
sensor assembly 120.
[0264] In step 1245, silver is deposited onto the reference
electrode 134 defined by the sensor substrate, and subsequently a
portion of the silver is converted to silver chloride to create a
Ag/AgCl electrode, which will serve as a reference electrode.
[0265] In step 1250, the sensor chemistry is deposited into the
sensor openings 592 as is discussed, for example, in method 1300
below.
[0266] In step 1255, laser singulation is performed to remove the
continuous monitoring sensors 120 from the glass substrate and from
each other. At this point, the bend or curl of continuous
monitoring sensors 120 may be inspected and confirmed for
conformance to the desired sensor bend or curl. For example, the
sensor bend or curl is measured for a predefined number of sensors
120 per plate using a high-powered microscope. In one embodiment,
the maximum bend radius R is no more than 1.375 inches (.about.35
mm). With this bend radius R, the continuous monitoring sensor 120
is maintained inside the cannula/needle 100 due to frictional
forces with the inside wall of the cannula/needle 100.
[0267] Exceeding the maximum bend radius may result in the
continuous monitoring sensor 120 falling out of the cannula. Bend
radius R results in part from the relative thicknesses of layers
500, 510, 550. Bend radius R also results in part from sequentially
curing layers 500, 510, 550 of multi-layer sensor substrate 500
starting with base layer 510, followed by middle layer 550, and
followed by top layer 580. The polyimide of base layer substrate
512 shrinks about 37% in thickness when cured. The polyimide of
middle layer substrate 552 and top layer 580 shrinks about 40% in
thickness when cured. Also, since top layer 580 (.about.55 .mu.m)
is approximately ten times as thick as either of base layer 510
(.about.10 .mu.m) or middle layer 550 (.about.10 .mu.m)), shrinkage
of top layer 550 during curing after base layer 510 and middle
layer 550 imparts bend radius R to multi-layer sensor substrate
500.
[0268] In one embodiment, continuous monitoring sensor 120 has a
length of about 18.42 mm with substrate proximal end portion 501
having a length of about 6.99 mm, substrate distal end portion 502
and assembly middle portion 503 each have a width of about 279
.mu.m, and substrate proximal end portion 501 has a width of about
711 .mu.m. With these dimensions, continuous monitoring sensor 120
is sized for use within a circular 25 gauge thin wall stainless
steel tubing or 27 gauge flattened thin wall stainless steel
tubing, both of which are shaped into a sharp forming needle 100.
The 25 gauge thin wall tubing has an outside diameter of about
0.020 inch (0.51 mm) nominal, and an inside diameter of about 0.015
inch (0.38 mm). The 27 gauge thin wall tubing has an outside
diameter of about 0.016 inch (0.41 mm) nominal, and an inside
diameter of about 0.012 inch (0.30 mm) nominal. Other gauges of
needles are acceptable and dimensions of multi-layer sensor
substrate 500 may be adjusted as needed for a tighter or looser fit
within a given needle.
[0269] An advantage of making continuous monitoring sensor 120 with
a plurality of layers (e.g., 510, 550, 580) in multi-layer sensor
substrate 500 is the ability to have more circuits (e.g., 522, 572)
in a predefined area. As such, continuous monitoring sensor 120 has
increased the available placement options for electrodes 130, 132,
133, 134. Also, a plurality of layers increases the ability to have
a larger number of electrode circuits in the same predefined area
thus permitting a variety of different types of electrodes on a
single continuous monitoring sensor 120. It is contemplated within
the scope of the present invention that continuous monitoring
sensor 120 has additional layers, such as a fourth, fifth, sixth,
or other additional layer (i.e. other "middle" layers between base
layer 510 and middle layer 550/top layer 580.
[0270] Sensor Chemistry Deposition Method:
[0271] Referring now to FIG. 55, a flowchart illustrates exemplary
steps of one method 1300 for depositing sensor chemistry as noted
above in step 1250 of method 1200. In step 1310, a multi-layer
sensor substrate 500 is provided as described above in steps
1205-1275 of method 1200, where multi-layer sensor substrate 500
defines two or more electrodes that are at least a first working
electrode and a reference electrode and where other electrodes are
selected from a counter electrode, a second working electrode, and
other analyte working electrodes, all being on one side of sensor
substrate 500. Typically, a plurality of multi-layer sensor
substrates 500 are provided as a group on the glass substrate.
[0272] In step 1315, liquid photoresist is applied to the sensor
substrate, such as by spin coating. The photoresist is exposed to
UV light in a predefined pattern, and the unexposed areas are
removed to define a pattern with openings in the photoresist
aligned with sensor openings 590 and/or sensor wells 592 of the
sensor substrate. Similarly, if negative photoresist is used, the
exposed areas are removed. It should be understood that embodiments
of the present invention are discussed as having electrodes 130,
132, 133, 134 on one side of the multi-layer sensor substrate 500;
a two-sided sensor is also contemplated as being within the scope
of the present invention.
[0273] In step 1320, a hydrogel membrane is deposited onto the
Ag/AgCl reference electrode 134 and counter electrode 133 by
dispensing a predefined amount of hydrogel membrane solution,
followed by UV curing and washing.
[0274] In step 1325, a layer of photoresist is deposited onto the
sensor substrate, exposed to UV light, and stripped to define
openings corresponding to the working electrode 130 and blank
electrodes 133 defined in the sensor substrate.
[0275] In step 1335, a poly-2-hydroxyethyl methacrylate (PHEMA)
membrane precursor solution is deposited onto the working electrode
130 and blank electrode 133, UV cured, washed and dried. It should
be understood by those skilled in the art that one of the two
electrodes is a glucose electrode and, accordingly, the PHEMA
membrane precursor solution for this electrode additionally
contains a glucose enzyme, preferably glucose oxidase. Optionally,
the PHEMA membrane precursor solution that contains the glucose
enzyme may also contain a predefined quantity of microspheres in
addition to the composite membrane described below. The predefined
quantity of microspheres is less than the amount of microspheres in
the composite membrane described below.
[0276] In step 1340, a composite membrane precursor solution is
deposited onto the working electrode 130 (e.g., a glucose
electrode) and the blank electrode 133, UV cured, and dried.
[0277] The preparation of the composite membrane precursor solution
will now be described. Microspheres are prepared from a material
having substantially no or little permeability to glucose but a
substantially high permeability to oxygen. The microspheres are
preferably prepared from PDMS (polydimethylsiloxane). The
microspheres are mixed with a hydrogel precursor that allows the
passage of glucose. While polyurethane hydrogels work, a PHEMA
precursor is preferred. The ratio of microspheres to hydrogel
determines the ratio of the glucose to oxygen permeability. Thus,
one of ordinary skill in the art can easily determine the ratio
that enables the desired dynamic range of glucose measurement at
the required low oxygen consumptions. It should be noted that if a
polyurethane hydrogel is used, the membrane is cured by evaporating
the solvent instead of using ultraviolet light.
[0278] In step 1345, additional PHEMA membrane precursor catalase
solution is optionally deposited onto the working electrode 130
(e.g., glucose) and blank electrode 133, UV cured, and dried. This
optional step adds catalase that prevents release of hydrogen
peroxide to the biological environment, reduces the flow rate
influence on sensor sensitivity, and prevents direct contact of the
microspheres surface to the biological environment.
[0279] In step 1350 and after the singulation step described in
FIG. 48, the continuous monitoring sensor 120 is installed into a
cannula/needle 100 according to the preferred embodiments
previously described.
[0280] Although the preferred embodiments of the present invention
have been described herein, the above description is merely
illustrative. Further modification of the invention herein
disclosed will occur to those skilled in the respective arts and
all such modifications are deemed to be within the scope of the
invention as defined by the appended claims.
* * * * *