U.S. patent application number 14/056882 was filed with the patent office on 2014-02-13 for method and system for providing calibration of an analyte sensor in an analyte monitoring system.
This patent application is currently assigned to Abbott Diabetes Care Inc.. The applicant listed for this patent is Abbott Diabetes Care Inc.. Invention is credited to Erwin Satrya Budiman, Kenneth J. Doniger, Gary Alan Hayter, John Charles Mazza, Songbiao Zhang.
Application Number | 20140046155 14/056882 |
Document ID | / |
Family ID | 39051710 |
Filed Date | 2014-02-13 |
United States Patent
Application |
20140046155 |
Kind Code |
A1 |
Hayter; Gary Alan ; et
al. |
February 13, 2014 |
Method and System for Providing Calibration of an Analyte Sensor in
an Analyte Monitoring System
Abstract
Method and apparatus for providing calibration of analyte sensor
including applying a control signal, detecting a measured response
to the control signal, determining a variance in the detected
measured response, and estimating a sensor sensitivity based on the
variance in the detected measured response is provided
Inventors: |
Hayter; Gary Alan; (Oakland,
CA) ; Doniger; Kenneth J.; (Menlo Park, CA) ;
Budiman; Erwin Satrya; (Fremont, CA) ; Zhang;
Songbiao; (Fremont, CA) ; Mazza; John Charles;
(Long Beach, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Abbott Diabetes Care Inc. |
Alameda |
CA |
US |
|
|
Assignee: |
Abbott Diabetes Care Inc.
Alameda
CA
|
Family ID: |
39051710 |
Appl. No.: |
14/056882 |
Filed: |
October 17, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13766673 |
Feb 13, 2013 |
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14056882 |
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|
12624377 |
Nov 23, 2009 |
8376945 |
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13766673 |
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11463582 |
Aug 9, 2006 |
7653425 |
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12624377 |
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Current U.S.
Class: |
600/345 ;
600/309 |
Current CPC
Class: |
A61B 5/14532 20130101;
A61B 5/1495 20130101; G01N 27/3274 20130101; A61B 5/0004 20130101;
A61B 2560/0223 20130101; A61B 5/14503 20130101; A61B 5/14546
20130101; A61B 5/1468 20130101; A61B 5/1473 20130101 |
Class at
Publication: |
600/345 ;
600/309 |
International
Class: |
A61B 5/1495 20060101
A61B005/1495; A61B 5/145 20060101 A61B005/145; A61B 5/1468 20060101
A61B005/1468 |
Claims
1. (canceled)
2. A method for determining whether an analyte sensor system is
functioning properly, the method comprising: applying a stimulus
signal to the analyte sensor; measuring a response to the stimulus
signal; estimating a value of a sensor property based on the signal
response; correlating the sensor property value with a
predetermined relationship of the sensor property and a
predetermined sensor sensitivity profile; and initiating an error
routine if the correlation does not exceed a predetermined
correlation threshold.
3. The method of claim 2, wherein correlating includes performing a
data association analysis.
4. The method of claim 2, wherein the error routine comprises
displaying a message to a user indicating that the analyte sensor
is not functioning properly.
5. The method of claim 2, wherein the sensor property is an
impedance of the sensor membrane.
6. A sensor system configured to implement the method of claim
2.
7. The sensor system of claim 6, wherein the sensor system
comprises instructions stored in computer memory, wherein the
instructions, when executed by one or more processors of the sensor
system, cause the sensor system to implement the method of claim
2.
8. A method for determining membrane damage of an analyte sensor
using a sensor system, comprising: applying a stimulus signal to an
analyte sensor; measuring a response to the stimulus signal;
calculating, using sensor electronics, an impedance based on the
signal response; determining, using the sensor electronics, whether
the impedance falls within a predefined level corresponding to
membrane damage; and initiating, using the sensor electronics, an
error routine if the impedance exceeds the predefined level.
9. The method of claim 8, wherein the error routine includes
triggering one or more of an audible alarm and a visual alarm on a
display screen.
10. The method of claim 8, wherein the stimulus signal has a
predetermined frequency.
11. The method of claim 8, wherein the stimulus signal comprises a
spectrum of frequencies.
12. The method of claim 8, wherein the calculated impedance
comprises a magnitude value and a phase value, and wherein the
determination comprises comparing the impedance magnitude value to
a predefined impedance magnitude threshold and the phase value to a
predefined phase threshold.
13. The method of claim 8, wherein the calculated impedance is a
complex impedance value.
14. A sensor system configured to implement the method of claim
8.
15. The sensor system of claim 14, wherein the sensor system
comprises instructions stored in computer memory, wherein the
instructions, when executed by one or more processors of the sensor
system, cause the sensor system to implement the method of claim
8.
16. A method for determining a property of a continuous analyte
sensor, the method comprising: applying a stimulus signal to a
first analyte sensor having a first working electrode and a first
reference electrode; measuring a signal response of the stimulus
signal using a second analyte sensor having a second working
electrode and a second reference electrode; and determining a
property of the first sensor by correlating the response to a
predetermined relationship.
17. The method of claim 16, further comprising generating sensor
data by applying a bias voltage to the first working electrode and
measuring a response to the bias voltage.
18. The method of claim 17, further comprising calibrating the
sensor data using the determined property.
19. The method of claim 16, wherein the determined property is one
of an impedance and a temperature.
20. The method of claim 16, further comprising determining sensor
membrane damage using the determined property.
21. A sensor system configured to implement the method of claim
16.
22. The sensor system of claim 21, wherein the sensor system
comprises instructions stored in computer memory, wherein the
instructions, when executed by one or more processors of the sensor
system, cause the sensor system to implement the method of claim
16.
23. A method for calibrating an analyte sensor, the method
comprising: applying a predetermined signal to an analyte sensor;
measuring a response to the applied signal; determining, using
sensor electronics, a change in impedance associated with a
membrane of the analyte sensor based on the measured response;
calculating a sensitivity change of the analyte sensor based on the
determined impedance; calculating a corrected sensitivity based on
the calculated sensitivity change and a previously used sensitivity
of the analyte sensor; and generating estimated analyte values
using the corrected sensitivity.
24. The method of claim 23, wherein calculating the sensitivity
change comprises applying a non-linear compensation function.
25. A sensor system configured to implement the method of claim
23.
26. The sensor system of claim 25, wherein the sensor system
comprises instructions stored in computer memory, wherein the
instructions, when executed by one or more processors of the sensor
system, cause the sensor system to implement the method of claim
23.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 13/766,673 filed Feb. 13, 2013, which is a
continuation of U.S. patent application Ser. No. 12/624,377 filed
Nov. 23, 2009, now U.S. Pat. No. 8,376,945, which is a continuation
of U.S. patent application Ser. No. 11/463,582 filed Aug. 9, 2006,
now U.S. Pat. No. 7,653,425, entitled "Method and System for
Providing Calibration of an Analyte Sensor in an Analyte Monitoring
System", the disclosures of each of which are incorporated herein
by reference for all purposes.
BACKGROUND
[0002] Analyte, e.g., glucose monitoring systems including
continuous and discrete monitoring systems generally include a
small, lightweight battery powered and microprocessor controlled
system which is configured to detect signals proportional to the
corresponding measured glucose levels using an electrometer, and RF
signals to transmit the collected data. One aspect of certain
analyte monitoring systems include a transcutaneous or subcutaneous
analyte sensor configuration which is, for example, partially
mounted on the skin of a subject whose analyte level is to be
monitored. The sensor cell may use a two or three-electrode (work,
reference and counter electrodes) configuration driven by a
controlled potential (potentiostat) analog circuit connected
through a contact system.
[0003] To obtain accurate data from the analyte sensor, calibration
is necessary. Typically, blood glucose measurements are
periodically obtained using, for example, a blood glucose meter,
and the measured blood glucose values are used to calibrate the
sensors. Indeed, the patient must calibrate each new analyte sensor
using for example, capillary blood glucose measurements. This may
be inconvenient for the patient.
[0004] In view of the foregoing, it would be desirable to have a
method and system for calibrating analyte sensors of an analyte
monitoring system that does not inconveniently require periodic
blood glucose measurements for sensor calibration.
SUMMARY OF THE INVENTION
[0005] In view of the foregoing, in accordance with the various
embodiments of the present invention, there is provided a method
and system for providing substantially automatic and substantially
real time calibration of analyte sensors for use in an analyte
monitoring system.
[0006] These and other objects, features and advantages of the
present invention will become more fully apparent from the
following detailed description of the embodiments, the appended
claims and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 illustrates a block diagram of a data monitoring and
management system for practicing one embodiment of the present
invention;
[0008] FIG. 2 is a block diagram of the transmitter unit of the
data monitoring and management system shown in FIG. 1 in accordance
with one embodiment of the present invention;
[0009] FIG. 3 is a block diagram of the receiver/monitor unit of
the data monitoring and management system shown in FIG. 1 in
accordance with one embodiment of the present invention;
[0010] FIG. 4 is a flowchart illustrating the analyte sensor
sensitivity estimation procedure in accordance with one embodiment
of the present invention;
[0011] FIG. 5 is a flowchart illustrating the analyte sensor
sensitivity estimation procedure in accordance with another
embodiment of the present invention;
[0012] FIG. 6 is a flowchart illustrating an analyte sensor
parameter estimation procedure in accordance with one embodiment of
the present invention;
[0013] FIG. 7A illustrates the transmission of the control signal
from the transmitter processor in accordance with one embodiment of
the present invention;
[0014] FIG. 7B illustrates the measured response to the control
signal from the transmitter processor shown in FIG. 7A in
accordance with one embodiment of the present invention;
[0015] FIG. 8 is a tabular illustration of a lookup table for
sensor sensitivity for use with the calibration procedure in
accordance with one embodiment of the present invention; and
[0016] FIG. 9 is a flowchart illustrating the analyte sensor
sensitivity estimation procedure in accordance with another
embodiment of the present invention.
DETAILED DESCRIPTION
[0017] As described in detail below, in accordance with the various
embodiments of the present invention, there is provided a method
and system for determining sensor sensitivity of an analyte sensor
which may be used to calibrate the analyte sensor in the analyte
monitoring system. In particular, within the scope of the present
invention, there is provided method and system for automatically
calibrating subcutaneous or transcutaneously positioned analyte
sensors such that the frequency of capillary blood glucose
measurement for calibration of the sensors may be minimized.
[0018] More specifically, FIG. 1 illustrates a data monitoring and
management system such as, for example, analyte (e.g., glucose)
monitoring system 100 in accordance with one embodiment of the
present invention. The subject invention is further described
primarily with respect to a glucose monitoring system for
convenience and such description is in no way intended to limit the
scope of the invention. It is to be understood that the analyte
monitoring system may be configured to monitor a variety of
analytes, e.g., lactate, and the like.
[0019] Analytes that may be monitored include, for example, acetyl
choline, amylase, bilirubin, cholesterol, chorionic gonadotropin,
creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine,
glucose, glutamine, growth hormones, hormones, ketones, lactate,
peroxide, prostate-specific antigen, prothrombin, RNA, thyroid
stimulating hormone, and troponin. The concentration of drugs, such
as, for example, antibiotics (e.g., gentamicin, vancomycin, and the
like), digitoxin, digoxin, drugs of abuse, theophylline, and
warfarin, may also be monitored.
[0020] The analyte monitoring system 100 includes a sensor 101, a
transmitter unit 102 coupled to the sensor 101, and a receiver unit
104 which is configured to communicate with the transmitter unit
102 via a communication link 103. The receiver unit 104 may be
further configured to transmit data to a data processing terminal
105 for evaluating the data received by the receiver unit 104.
Moreover, the data processing terminal in one embodiment may be
configured to receive data directly from the transmitter unit 102
via a communication link 106 which may optionally be configured for
bi-directional communication.
[0021] Only one sensor 101, transmitter unit 102, receiver unit
104, communication link 103, and data processing terminal 105 are
shown in the embodiment of the analyte monitoring system 100
illustrated in FIG. 1. However, it will be appreciated by one of
ordinary skill in the art that the analyte monitoring system 100
may include one or more sensor 101, transmitter unit 102, receiver
unit 104, communication link 103, and data processing terminal 105.
Moreover, within the scope of the present invention, the analyte
monitoring system 100 may be a continuous monitoring system, or
semi-continuous, or a discrete monitoring system. In a
multi-component environment, each device is configured to be
uniquely identified by each of the other devices in the system so
that communication conflict is readily resolved between the various
components within the analyte monitoring system 100.
[0022] In one embodiment of the present invention, the sensor 101
is physically positioned in or on the body of a user whose analyte
level is being monitored. The sensor 101 may be configured to
continuously sample the analyte level of the user and convert the
sampled analyte level into a corresponding data signal for
transmission by the transmitter unit 102. In one embodiment, the
transmitter unit 102 is mounted on the sensor 101 so that both
devices are positioned on the user's body. The transmitter unit 102
performs data processing such as filtering and encoding on data
signals, each of which corresponds to a sampled analyte level of
the user, for transmission to the receiver unit 104 via the
communication link 103.
[0023] In one embodiment, the analyte monitoring system 100 is
configured as a one-way RF communication path from the transmitter
unit 102 to the receiver unit 104. In such embodiment, the
transmitter unit 102 transmits the sampled data signals received
from the sensor 101 without acknowledgement from the receiver unit
104 that the transmitted sampled data signals have been received.
For example, the transmitter unit 102 may be configured to transmit
the encoded sampled data signals at a fixed rate (e.g., at one
minute intervals) after the completion of the initial power on
procedure. Likewise, the receiver unit 104 may be configured to
detect such transmitted encoded sampled data signals at
predetermined time intervals. Alternatively, the analyte monitoring
system 100 may be configured with a bi-directional RF (or
otherwise) communication between the transmitter unit 102 and the
receiver unit 104.
[0024] Additionally, in one aspect, the receiver unit 104 may
include two sections. The first section is an analog interface
section that is configured to communicate with the transmitter unit
102 via the communication link 103. In one embodiment, the analog
interface section may include an RF receiver and an antenna for
receiving and amplifying the data signals from the transmitter unit
102, which are thereafter, demodulated with a local oscillator and
filtered through a band-pass filter. The second section of the
receiver unit 104 is a data processing section which is configured
to process the data signals received from the transmitter unit 102
such as by performing data decoding, error detection and
correction, data clock generation, and data bit recovery.
[0025] In operation, upon completing the power-on procedure, the
receiver unit 104 is configured to detect the presence of the
transmitter unit 102 within its range based on, for example, the
strength of the detected data signals received from the transmitter
unit 102 or a predetermined transmitter identification information.
Upon successful synchronization with the corresponding transmitter
unit 102, the receiver unit 104 is configured to begin receiving
from the transmitter unit 102 data signals corresponding to the
user's detected analyte level. More specifically, the receiver unit
104 in one embodiment is configured to perform synchronized time
hopping with the corresponding synchronized transmitter unit 102
via the communication link 103 to obtain the user's detected
analyte level.
[0026] Referring again to FIG. 1, the data processing terminal 105
may include a personal computer, a portable computer such as a
laptop or a handheld device (e.g., personal digital assistants
(PDAs)), and the like, each of which may be configured for data
communication with the receiver via a wired or a wireless
connection. Additionally, the data processing terminal 105 may
further be connected to a data network (not shown) for storing,
retrieving and updating data corresponding to the detected analyte
level of the user.
[0027] Within the scope of the present invention, the data
processing terminal 105 may include an infusion device such as an
insulin infusion pump or the like, which may be configured to
administer insulin to patients, and which may be configured to
communicate with the receiver unit 104 for receiving, among others,
the measured analyte level. Alternatively, the receiver unit 104
may be configured to integrate an infusion device therein so that
the receiver unit 104 is configured to administer insulin therapy
to patients, for example, for administering and modifying basal
profiles, as well as for determining appropriate boluses for
administration based on, among others, the detected analyte levels
received from the transmitter unit 102.
[0028] Additionally, the transmitter unit 102, the receiver unit
104 and the data processing terminal 105 may each be configured for
bi-directional wireless communication such that each of the
transmitter unit 102, the receiver unit 104 and the data processing
terminal 105 may be configured to communicate (that is, transmit
data to and receive data from) with each other via the wireless
communication link 103. More specifically, the data processing
terminal 105 may in one embodiment be configured to receive data
directly from the transmitter unit 102 via the communication link
106, where the communication link 106, as described above, may be
configured for bi-directional communication.
[0029] In this embodiment, the data processing terminal 105 which
may include an insulin pump, may be configured to receive the
analyte signals from the transmitter unit 102, and thus,
incorporate the functions of the receiver 103 including data
processing for managing the patient's insulin therapy and analyte
monitoring. In one embodiment, the communication link 103 may
include one or more of an RF communication protocol, an infrared
communication protocol, a Bluetooth enabled communication protocol,
an 802.11x wireless communication protocol, or an equivalent
wireless communication protocol which would allow secure, wireless
communication of several units (for example, per HIPAA
requirements) while avoiding potential data collision and
interference.
[0030] FIG. 2 is a block diagram of the transmitter of the data
monitoring and detection system shown in FIG. 1 in accordance with
one embodiment of the present invention. Referring to the Figure,
the transmitter unit 102 in one embodiment includes an analog
interface 201 configured to communicate with the sensor 101 (FIG.
1), a user input 202, and a temperature detection section 203, each
of which is operatively coupled to a transmitter processor 204 such
as a central processing unit (CPU). There are provided four
contacts, three of which are electrodes--work electrode, guard
contact, reference electrode, and counter electrode, each
operatively coupled to the analog interface 201 of the transmitter
unit 102 for connection to the sensor unit 101 (FIG. 1). In one
embodiment, each of the work electrode, guard contact, reference
electrode, and counter electrode may be made using a conductive
material that is either printed or etched, for example, such as
carbon which may be printed, or metal foil (e.g., gold) which may
be etched.
[0031] Further shown in FIG. 2 are a transmitter serial
communication section 205 and an RF transmitter 206, each of which
is also operatively coupled to the transmitter processor 204.
Moreover, a power supply 207 such as a battery is also provided in
the transmitter unit 102 to provide the necessary power for the
transmitter unit 102. Additionally, as can be seen from the Figure,
clock 208 is provided to, among others, supply real time
information to the transmitter processor 204.
[0032] In one embodiment, a unidirectional input path is
established from the sensor 101 (FIG. 1) and/or manufacturing and
testing equipment to the analog interface 201 of the transmitter
unit 102, while a unidirectional output is established from the
output of the RF transmitter 206 of the transmitter unit 102 for
transmission to the receiver unit 104. In this manner, a data path
is shown in FIG. 2 between the aforementioned unidirectional input
and output via a dedicated link 209 from the analog interface 201
to serial communication section 205, thereafter to the processor
204, and then to the RF transmitter 206. As such, in one
embodiment, via the data path described above, the transmitter unit
102 is configured to transmit to the receiver unit 104 (FIG. 1),
via the communication link 103 (FIG. 1), processed and encoded data
signals received from the sensor 101 (FIG. 1). Additionally, the
unidirectional communication data path between the analog interface
201 and the RF transmitter 206 discussed above allows for the
configuration of the transmitter unit 102 for operation upon
completion of the manufacturing process as well as for direct
communication for diagnostic and testing purposes.
[0033] As discussed above, the transmitter processor 204 is
configured to transmit control signals to the various sections of
the transmitter unit 102 during the operation of the transmitter
unit 102. In one embodiment, the transmitter processor 204 also
includes a memory (not shown) for storing data such as the
identification information for the transmitter unit 102, as well as
the data signals received from the sensor 101. The stored
information may be retrieved and processed for transmission to the
receiver unit 104 under the control of the transmitter processor
204. Furthermore, the power supply 207 may include a commercially
available battery.
[0034] The transmitter unit 102 is also configured such that the
power supply section 207 is capable of providing power to the
transmitter for a minimum of about three months of continuous
operation after having been stored for about eighteen months in a
low-power (non-operating) mode. In one embodiment, this may be
achieved by the transmitter processor 204 operating in low power
modes in the non-operating state, for example, drawing no more than
approximately 1 .mu.A of current. Indeed, in one embodiment, the
final step during the manufacturing process of the transmitter unit
102 may place the transmitter unit 102 in the lower power,
non-operating state (i.e., post-manufacture sleep mode). In this
manner, the shelf life of the transmitter unit 102 may be
significantly improved.
[0035] Moreover, as shown in FIG. 2, while the power supply unit
207 is shown as coupled to the processor 204, and as such, the
processor 204 is configured to provide control of the power supply
unit 207, it should be noted that within the scope of the present
invention, the power supply unit 207 is configured to provide the
necessary power to each of the components of the transmitter unit
102 shown in FIG. 2.
[0036] Referring back to FIG. 2, the power supply section 207 of
the transmitter unit 102 in one embodiment may include a
rechargeable battery unit that may be recharged by a separate power
supply recharging unit (for example, provided in the receiver unit
104) so that the transmitter unit 102 may be powered for a longer
period of usage time. Moreover, in one embodiment, the transmitter
unit 102 may be configured without a battery in the power supply
section 207, in which case the transmitter unit 102 may be
configured to receive power from an external power supply source
(for example, a battery) as discussed in further detail below.
[0037] Referring yet again to FIG. 2, the temperature detection
section 203 of the transmitter unit 102 is configured to monitor
the temperature of the skin near the sensor insertion site. The
temperature reading is used to adjust the analyte readings obtained
from the analog interface 201. The RF transmitter 206 of the
transmitter unit 102 may be configured for operation in the
frequency band of 315 MHz to 322 MHz, for example, in the United
States. Further, in one embodiment, the RF transmitter 206 is
configured to modulate the carrier frequency by performing
Frequency Shift Keying and Manchester encoding. In one embodiment,
the data transmission rate is 19,200 symbols per second, with a
minimum transmission range for communication with the receiver unit
104.
[0038] Additional detailed description of the continuous analyte
monitoring system, its various components including the functional
descriptions of the transmitter are provided in U.S. Pat. No.
6,175,752 issued Jan. 16, 2001 entitled "Analyte Monitoring Device
and Methods of Use", and in application Ser. No. 10/745,878 filed
Dec. 26, 2003 entitled "Continuous Glucose Monitoring System and
Methods of Use", each assigned to the Assignee of the present
application.
[0039] FIG. 3 is a block diagram of the receiver/monitor unit of
the data monitoring and management system shown in FIG. 1 in
accordance with one embodiment of the present invention. Referring
to FIG. 3, the receiver unit 104 includes a blood glucose test
strip interface 301, an RF receiver 302, an input 303, a
temperature detection section 304, and a clock 305, each of which
is operatively coupled to a receiver processor 307. As can be
further seen from the Figure, the receiver unit 104 also includes a
power supply 306 operatively coupled to a power conversion and
monitoring section 308. Further, the power conversion and
monitoring section 308 is also coupled to the receiver processor
307. Moreover, also shown are a receiver serial communication
section 309, and an output 310, each operatively coupled to the
receiver processor 307.
[0040] In one embodiment, the test strip interface 301 includes a
glucose level testing portion to receive a manual insertion of a
glucose test strip, and thereby determine and display the glucose
level of the test strip on the output 310 of the receiver unit 104.
This manual testing of glucose can be used to calibrate sensor 101.
The RF receiver 302 is configured to communicate, via the
communication link 103 (FIG. 1) with the RF transmitter 206 of the
transmitter unit 102, to receive encoded data signals from the
transmitter unit 102 for, among others, signal mixing,
demodulation, and other data processing. The input 303 of the
receiver unit 104 is configured to allow the user to enter
information into the receiver unit 104 as needed. In one aspect,
the input 303 may include one or more keys of a keypad, a
touch-sensitive screen, or a voice-activated input command unit.
The temperature detection section 304 is configured to provide
temperature information of the receiver unit 104 to the receiver
processor 307, while the clock 305 provides, among others, real
time information to the receiver processor 307.
[0041] Each of the various components of the receiver unit 104
shown in FIG. 3 is powered by the power supply 306 which, in one
embodiment, includes a battery. Furthermore, the power conversion
and monitoring section 308 is configured to monitor the power usage
by the various components in the receiver unit 104 for effective
power management and to alert the user, for example, in the event
of power usage which renders the receiver unit 104 in sub-optimal
operating conditions. An example of such sub-optimal operating
condition may include, for example, operating the vibration output
mode (as discussed below) for a period of time thus substantially
draining the power supply 306 while the processor 307 (thus, the
receiver unit 104) is turned on. Moreover, the power conversion and
monitoring section 308 may additionally be configured to include a
reverse polarity protection circuit such as a field effect
transistor (FET) configured as a battery activated switch.
[0042] The serial communication section 309 in the receiver unit
104 is configured to provide a bi-directional communication path
from the testing and/or manufacturing equipment for, among others,
initialization, testing, and configuration of the receiver unit
104. Serial communication section 104 can also be used to upload
data to a computer, such as time-stamped blood glucose data. The
communication link with an external device (not shown) can be made,
for example, by cable, infrared (IR) or RF link. The output 310 of
the receiver unit 104 is configured to provide, among others, a
graphical user interface (GUI) such as a liquid crystal display
(LCD) for displaying information. Additionally, the output 310 may
also include an integrated speaker for outputting audible signals
as well as to provide vibration output as commonly found in
handheld electronic devices, such as mobile telephones presently
available. In a further embodiment, the receiver unit 104 also
includes an electro-luminescent lamp configured to provide
backlighting to the output 310 for output visual display in dark
ambient surroundings.
[0043] Referring back to FIG. 3, the receiver unit 104 in one
embodiment may also include a storage section such as a
programmable, non-volatile memory device as part of the processor
307, or provided separately in the receiver unit 104, operatively
coupled to the processor 307. The processor 307 is further
configured to perform Manchester decoding as well as error
detection and correction upon the encoded data signals received
from the transmitter unit 102 via the communication link 103.
[0044] Referring back to the Figures, as described in further
detail below, in one embodiment of the present invention, the
transmitter processor 204 may be configured to transmit a control
signal to the analog interface 201 to determine the poise voltage
between the work electrode and the reference electrode of the
sensor unit 101, each of which are operatively coupled to the
analog interface 201 of the transmitter unit 102.
[0045] More specifically, in one embodiment, a control processor
component of the transmitter unit 102 processor 204 is configured
to provide a perturbation control signal to the analog interface
201. The analog interface 201 is configured to translate the
received perturbation control signal to a perturbation that affects
the sensor response. For example, the control signal in one
embodiment may be configured to control the voltage level that is
applied to the sensor 101 between the work and reference electrodes
(i.e., the poise voltage). In one embodiment, the analog interface
201 of the transmitter unit 102 is configured to translate the
sensor response to the perturbation to a corresponding response
signal that is acquired by the signal processing component of the
processor 204 of the transmitter unit 102. The signal processing
component of the processor 204 in the transmitter unit 102 in one
embodiment may be configured to determine the desired sensor
parameter estimation which is transmitted to the receiver unit 104.
Alternatively, the signal processing component of the processor 204
in the transmitter unit 102 may be configured to preprocess the
data, which are then transmitted to the receiver unit for sensor
parameter estimation determination.
[0046] More specifically, FIG. 4 is a flowchart illustrating
analyte sensor sensitivity estimation procedure in accordance with
one embodiment of the present invention. Referring to FIG. 4, at
step 410, the transmitter processor 204 (FIG. 2) in one embodiment
is configured to provide a control signal to the analog interface
201 (for example a poise voltage control circuit) of the
transmitter unit 102. In one aspect, the control signal provides a
perturbation input to determine the poise voltage between the work
electrode and the reference electrode of the sensor unit 101. In
one aspect, the poise voltage may be in the range of approximately
-600 mV and 600 mV, and the analog interface 201 may be configured
to control the poise voltage and apply the poise voltage to the
electrodes of the sensor unit 101.
[0047] One embodiment of the control signal perturbations is shown
in FIG. 7A which illustrates the control signal from the
transmitter processor 204 so as to provide a poise voltage waveform
that is a square wave of 50% duty cycle with a one minute time
period interval. In one embodiment, the poise voltage square wave
amplitude may be switched from 40 mV to -600mV from, for example,
the normal operating poise voltage to a predetermined level such as
-600 mV which effectively shuts down the current signal on the work
electrode.
[0048] Referring back to FIG. 4, at step 420, the analog interface
201 in one embodiment is configured to determine a measured
response to the received control signal, for example, a voltage
signal which is substantially proportional to the current signal
level on the work electrode of the sensor unit 101. An aspect of
the measured response is illustrated in FIG. 7B. As shown, in one
aspect, the current signal level is associated with the analyte
level of the patient and may be modulated by the poise voltage
perturbations driven by the control signal from the transmitter
processor 204. Thereafter at step 430, the transmitter processor
204 may be optionally configured to synchronize the measured
response from the analog interface 201 with the control signal. The
transmitter processor 204 may be further configured to store the
measured response and the associated control signal in a storage
unit (not shown) such as a memory device.
[0049] Referring again to FIG. 4, the transmitter processor 204 in
one embodiment is configured to determine the difference or
variance in the measured response based on the control signal 440,
and the sensor sensitivity may be determined based on the
determined difference in measured response 450. That is, in one
embodiment, the difference in measured response is compared to a
look up table stored, for example, in the transmitter processor 204
memory unit which includes calculated measured response difference
for the sensor based on characteristics of the sensor unit 101.
[0050] By way of an example, for a measured response difference of
47 analog to digital counts, the lookup table for sensor
sensitivity (FIG. 8) indicates 34.5 pA/(mg/dL) for the sensor.
Then, the determined sensor sensitivity may be applied to the work
electrode current to determine the corresponding calibrated analyte
value. That is, the calibrated analyte value may be determined by
dividing the work electrode current signal by the sensor
sensitivity.
[0051] FIG. 5 is a flowchart illustrating the analyte sensor
sensitivity estimation procedure in accordance with another
embodiment of the present invention. Referring to FIG. 5, at step
510, a perturbation control signal is applied to the sensor 101
(FIG. 1), and then the response to the perturbation control signal
is measured at step 520. Based on the measured response to the
perturbation control signal, at step 530, the sensor parameter(s)
is estimated and at step 540, the analyte level is estimated based
on the measured response to the perturbation control signal. In one
embodiment, the procedure shown in FIG. 5 is repeated
continuously.
[0052] In accordance with the various embodiments of the present
invention, different estimates may be determined including, for
example, estimation of sensor properties such as sensitivity and
response time, the analyte level, and analyte level
validity/accuracy. In one embodiment, there are several mechanisms
that may be used to perturb the sensor 101 (FIG. 1), for example,
the variable poise voltage. In a further aspect, the one or more of
the perturbation control signals may include, for example, square
waves. Also, in one aspect, the one or more physical sensor
responses that are measured may include, for example, work
electrode current variation due to poise voltage perturbation. In
addition, signal processing may be used in one embodiment to
estimate the sensor parameter or analyte level from the sensor
response to the perturbation as described above.
[0053] FIG. 6 is a flowchart illustrating an analyte sensor
parameter estimation procedure in accordance with one embodiment of
the present invention. Referring to FIG. 6, a control signal is
applied, for example, to the analog interface 201 of the
transmitter unit 102 (FIG. 1). That is, in one embodiment, the
processor 204 of the transmitter unit 102 may be configured to
provide a control signal to a poise voltage control circuit (for
example, incorporated in the processor 204 of the transmitter unit
102 as shown in FIG. 2, but which may, in one embodiment, be
separately provided within the transmitter unit 102) of the
transmitter unit 102.
[0054] In one aspect, the control signal may be configured to
provide a perturbation input signal to determine the poise voltage
between the work electrode and the reference electrode of the
sensor unit 101. In one embodiment, the poise voltage may be in the
range of approximately -600 mV and 600 mV, and the analog interface
201 may be configured to control the poise voltage and apply the
poise voltage to the electrodes of the sensor unit 101.
[0055] As described in further detail below, an embodiment of the
control signal perturbations is shown in FIG. 7A which illustrates
the control signal from the processor 204 (FIG. 2) to provide a
poise voltage waveform that is a square wave of 50% duty cycle with
a one minute time period interval. Referring to FIG. 7A, in one
embodiment, the poise voltage square wave amplitude may be switched
from 40 mV to -600 mV from, for example, the normal operating poise
voltage to a predetermined level such as -600 mV which effectively
shuts down the current signal on the work electrode.
[0056] Referring back to FIG. 6, the analog interface 201 in one
embodiment is configured to determine a measured response to the
received control signal, for example, a voltage signal which is
substantially proportional to the current signal level on the work
electrode of the sensor unit 101 (FIG. 1). As discussed in further
detail below, one embodiment of the measured response is shown in
FIG. 7B. Referring to FIG. 7B, in one embodiment, the average
signal level for half of the duty cycle is associated with the
analyte level of the patient, but the transient within the
half-duty cycle period, caused by the poise voltage perturbations
driven by the control signal from the transmitter processor 204, is
associated with the sensitivity parameter of the sensor 101. The
transmitter processor 204 may be further configured to store the
measured response and the associated control signal in a storage
unit (not shown) such as a memory device.
[0057] Referring again to FIG. 6, the transmitter processor 204 in
one embodiment is configured to determine the amplitude difference
of the transient from the start of the half-duty cycle to the end
(referred to sometimes as the "on" period) in the measured response
630, and the sensor sensitivity may be determined based on the
determined difference in the response 640. That is, in one
embodiment, the difference in measured response is compared to a
predetermined sensor parameter such as sensor sensitivity that may
be stored in a look up table, for example, in the transmitter
processor 204 memory unit. In one aspect, the look up table may
include a calculated measured response difference for the sensor
unit 101 and corresponding sensor sensitivities based on
characteristics of the sensor unit 101.
[0058] In one embodiment, the transmitter may be configured to
determine this sensitivity value once per minute, and to transmit
the sensitivity value it to the receiver unit 104 (FIG. 1) in
addition to data or signal corresponding to the work current signal
level, determined at the end of the "on" period, and skin
temperature.
[0059] In one embodiment, the receiver unit 104 (FIG. 1) may be
configured to apply the determined sensor sensitivity to the
temperature compensated work electrode current signal in order to
determine the corresponding calibrated analyte value or level. That
is, the calibrated analyte value may be determined by dividing the
temperature compensated work electrode current signal by the
determined sensor sensitivity. In one aspect, a time-series of the
calibrated analyte values may be acquired by the receiver unit 104
(FIG. 1) in real-time, and may be used to determine analyte
rate-of-change and other analyte signal metrics and/or statistics.
In addition, the calibrated analyte values may also be used to
drive alarms or alerts that inform the patient whose analyte is
being monitored of analyte level conditions that require attention.
In addition, in accordance with one aspect of the present
invention, the receiver unit 104 may be configured to determine
whether the sensor sensitivity range is within a valid range.
[0060] FIG. 7A illustrates the transmission of the control signal
from the transmitter processor in accordance with one embodiment of
the present invention. More particularly, FIG. 7A illustrates the
poise voltage square wave with 50% duty cycle with one minute time
periods is shown, where the poise voltage square wave amplitude is
switched from 40 mV to -600 mV as in normal operating mode. FIG. 7B
illustrates the measured response to the control signal from the
transmitter processor shown in FIG. 7A in accordance with one
embodiment of the present invention. More specifically, the
measured response which is associated with the analyte level
measured by the sensor unit 101 from the interstitial fluid of a
patient as modulated by the control signal from the transmitter
processor 204 is illustrated with one minute time periods
[0061] FIG. 8 is a tabular illustration of a lookup table for
sensor sensitivity for use with the calibration procedure in
accordance with one embodiment of the present invention. More
specifically, in one embodiment, the lookup table shown in FIG. 8
is stored in a memory unit (not shown) of the transmitter unit 102
(or alternatively, in the transmitter processor 204) and may be
accessed by the transmitter processor 204 to retrieve a
corresponding sensitivity value associated with the determined
measured response difference.
[0062] FIG. 9 is a flowchart illustrating the analyte sensor
sensitivity estimation procedure in accordance with another
embodiment of the present invention. Referring to FIG. 9, in one
embodiment, a control signal from the transmitter processor 204
(FIG. 2) is provided 910 to the transmitter unit 102 analog
interface 201, and a response to the applied control signal is
determined 920. Thereafter, the difference or variance in the
determined response to the control signal between the beginning and
end of the half duty cycle is determined 930. As can be seen, in
one embodiment, steps 910 to 930 are substantially similar to steps
610 to 630, respectively described above.
[0063] Referring back to FIG. 9, after determining the measured
response variance or difference between the beginning and end of
the half duty cycle, it is determined whether the number of
transmitted or applied control signals exceed a predetermined
number or count 940. If it is determined that the number of
transmitted or applied control signals do not exceed the
predetermined number or count, then a control signal counter (for
example, provided in the transmitter unit 102) is incremented by
one count, and the routine returns to the beginning where another
control signal is provided to the analog interface 201 of the
transmitter unit 102.
[0064] On the other hand, if it is determined that the number of
transmitted or applied control signals exceed the predetermined
number or count, then the sensor sensitivity may be determined
based on the determined difference in the response. That is, as
discussed above, the difference in measured response in one
embodiment is compared to a predetermined sensor parameter such as
sensor sensitivity that may be stored in a look up table, for
example, in the transmitter processor 204 memory unit. In one
aspect, the look up table may include a calculated measured
response difference for the sensor and corresponding sensor
sensitivities based on characteristics of the sensor. Furthermore,
as discussed above, in one embodiment, the calibrated analyte value
or level may be determined by, for example, dividing the
corresponding sensor signal (e.g., work electrode current signal)
level by the determined sensor sensitivity value.
[0065] Within the scope of the present invention, the perturbations
to the analyte sensors may be provided by, for example, altering
the poise voltage in time. Alternatively, an additional electrical
current signal may be provided to the sensor work or counter
electrodes via an AC coupling, where the level of the additional
electrical current signal may be varied in time by the control
signal in a manner similar as discussed above. Still in accordance
with another embodiment, the work/counter electrode current path
may be opened and closed in a time varying manner controlled by the
control signal. Yet still another embodiment may provide a variable
resistance in the work/counter electrode current path, where the
variable resistance is varied in time as controlled by the control
signal.
[0066] In another aspect of the present invention, the
transcutaneously positioned sensor may be perturbed with a
mechanical transducer controlled in time and amplitude by a
predetermined control signal. In one embodiment, mechanical
transducers may include those that can provide physical signals of
vibration, acoustics, thermal or electro-magnetic media, for
example. Broadly, any suitable mechanism to apply perturbations to
the transcutaneously positioned sensor may be used to the extent
that the measured response may be analyzed by the signal processing
component such as, for example, the transmitter unit processor 204
to estimate one or more sensor properties based on the signal
response induced by the perturbations. For example, vibration
perturbations may induce fluctuations in the sensor membrane that
could be detected in the measured response transients, which may be
correlated with membrane thickness and thus provide a measure of
the sensitivity of the sensor.
[0067] In addition, in accordance with the various embodiments of
the present invention, there are provided a variety of time-varying
controls signals that may be applied, along with a variety of
techniques used to analyze the measured response and estimate the
sensor parameter of interest. Some of these control signals may be
appropriate to induce a measured response that is more informative
about a specific sensor parameter than other control signals, and
some control signals may be more practical to implement than
others. As discussed previously, a square-wave control signal may
be employed in one embodiment. Variations in this type of control
signal may be suitably used where the positive and negative
amplitudes are at different levels, the duty cycle is other than
50%, or the period is other than 1 minute.
[0068] In another embodiment of the present invention, a feedback
mechanism may be provided where the duty cycle is varied to achieve
a desired response, such as a specific transient response time. In
this case, the final duty cycle is the parameter that is correlated
with the sensor parameter to be estimated. This feedback technique
may be extended to other types of control signals, mentioned below,
and other characteristics of the signal such as phase, amplitude
and frequency may be varied to achieve a desired response.
[0069] Alternatively, a sine wave may be used as the control signal
discussed above rather than a square wave. Still alternatively, a
series of sine waves at different frequencies, or a chirp signal
may be used as control signals in one embodiment of the present
invention. The measured response of these perturbation signals may
then be analyzed using standard spectral analysis techniques. Based
on the spectral analysis, metrics may be determined that are
correlated with the sensor parameter to be estimated.
[0070] In accordance with yet another embodiment, an impulse
signal, or a series of impulse signals may be alternatively used as
control signals. The measured response of these perturbation
signals may be analyzed using known impulse response analysis
techniques. For example, the maximum height of the measured
response may be used to determine the associated sensor
sensitivity. Alternatively, other signal metrics such as the time
to reach the maximum height of the measured response, the area
under the curve of the measured response, the slope of the measured
response may be correlated with the sensor parameter to be
estimated.
[0071] In still another embodiment, pseudo-random modulation
similar to those used in spread-spectrum communication systems may
be used as the control signals. The measured response of these
perturbation signals may be analyzed using known spread-spectrum
analysis techniques. Based on this analysis, metrics may be
determined that are correlated with the sensor parameter to be
estimated. In addition, the response signal may be demodulated
using spread-spectrum techniques to recover the analyte level.
[0072] For some of the control signal/response measurement analysis
techniques discussed above, the relative phase between the control
signal and the measured response may be used to analyze the
measured response to the perturbation. For some of the control
signal/response measurement analysis techniques discussed above,
multiple metrics may be determined. One or more of these metrics
may be used to estimate the sensor parameter of interest. For
example, in one embodiment, a multidimensional table lookup may be
used where one dimension includes the sensor parameter of interest,
and the other dimensions may each be associated with a different
metric that characterizes the measured response. More specifically,
by way of illustration, in the impulse response approach described
above, both the maximum height and the time to reach the height of
the measured response may be determined. In this case, a three
dimensional lookup table may be used.
[0073] As discussed above, in one embodiment, a lookup table may be
used to correlate a metric associated with the measured response
with a sensor parameter of interest (for example, sensitivity).
Alternatively, a mathematical function that relates the measured
response metric with the sensor parameter may be used. The sensor
parameter may then be determined based on the measured response
metric as an input. In another aspect, the estimate of the sensor
parameter may be determined for many measurements using, for
example, the least squares approach.
[0074] In addition, within the scope of the present invention, the
control signal may be transmitted to the analog interface 201 at
predetermined time periods during the life of the sensor.
Alternatively, the transmitter processor 204 may be configured to
transmit the control signal only during the time periods when
sensor calibration is desired or if some other factor, such as a
detection of sensitivity instability, determines that sensor
calibration is required.
[0075] Moreover, in one embodiment, other system parameters in
addition to sensitivity may be associated with the measured
response from the analog interface 201 in response to the control
signal from the transmitter processor 204. These include, but are
not limited to, sensor response time, sensor response linearity,
sensitivity stability and sensor failure. Accurately estimated
sensor response time can be useful for incorporation into
algorithms that compensate for errors due to lag in the analyte
measurement system. Knowledge of the non-linearity in the sensor
response (non-linearity means that the sensitivity is not constant
over the entire range to measured response) allows for compensation
of errors caused by this non-linearity.
[0076] Detection of sensitivity instability (that is, detection
when the sensitivity has changed value) may be used to accurately
determine the new sensitivity. For example, if instability has been
detected by the signal processing component, it can direct the
control processing component such as the transmitter unit processor
204 to initiate a control signal that is more appropriate to
accurately estimating the sensitivity. Also, detecting a sudden,
substantial change in sensitivity may be used to identify that a
sensor may have failed.
[0077] While the control signal may be used to determine the sensor
sensitivity, in one embodiment, the resulting modulation in the
measured response may be removed by, for example, one or more
signal filters to recover the glucose signal. In one aspect, a
standard signal filter may be used to remove the high frequency
content of the signal due to modulation by the perturbation control
signal, and recover the lower frequency content that represents the
analyte level. In another aspect, the modulation may be deconvolved
using the control signal, the calculated sensor response and the
estimated sensitivity.
[0078] Furthermore, there are several approaches to measure a
sensor's response to the perturbation signals in order to estimate
desired properties or characteristics of the sensor. For example,
in one embodiment, the electrical current that flows through the
work (and counter) electrode may be measured. Alternatively, the
perturbation response in the counter electrode voltage may be
alternatively measured. The measured counter voltage response may
be analyzed using same or similar techniques as the measured work
current response.
[0079] In another embodiment, both work current and counter voltage
responses may be measured and analyzed.
[0080] In the manner described above, within the scope of the
present invention, there is provided method and system for
performing calibration of analyte sensors based on the sensor
dynamic behavior and on a substantially real time basis such that
sensor calibrations based on blood glucose measurements may be
minimized further to improve the accuracy of the analyte sensor
data.
[0081] In accordance with the various embodiments of the present
invention, the transmitter processor 204 may include a
microcontroller, or alternatively, may be implemented with digital
logic such as a gate array or similar logic devices. In addition,
in one embodiment, the measured response variance as well as the
estimated sensor sensitivity determined by the transmitter
processor 204 may be transmitted to the receiver unit 104 (FIG. 1)
in the analyte monitoring system 100 in addition to the analyte
sensor measurements (for example, the work electrode current
measurements detected by the sensor unit 101).
[0082] In a further aspect, some of the processing may be performed
by the receiver unit 104
[0083] (FIG. 1) rather than by the transmitter processor 204 such
that the transmitter unit 102 may be configured to periodically
transmit the measured response variance to the receiver unit 104,
and the receiver unit processing and storage unit 307 (FIG. 3) may
be configured to perform the sensor sensitivity determination based
on the lookup table which may be stored in a memory device (not
shown) in the receiver unit 104.
[0084] A method of calibrating an analyte sensor in one embodiment
includes applying a control signal, detecting a measured response
to the control signal, determining a variance in the detected
measured response, and estimating a sensor sensitivity based on the
variance in the detected measured response.
[0085] The level of the control signal may in one embodiment vary
in time.
[0086] In one aspect, the control signal may include a square wave
signal, where the square wave signal may be applied to a poise
voltage.
[0087] In a further aspect, detecting the measured response may
include determining a work electrode current signal.
[0088] In still another aspect, the variance may be determined
based on comparing the difference between the beginning and end of
the half duty cycle of the measured response to the control
signal.
[0089] Moreover, estimating the sensor sensitivity may include
retrieving a predetermined sensor sensitivity corresponding to the
determined variance in the detected measured response.
[0090] The method may also include determining a validity of the
estimated sensor sensitivity.
[0091] In addition, the method may also include determining analyte
level based on the estimated sensor sensitivity.
[0092] The sensor in one embodiment may include an analyte
sensor.
[0093] An analyte sensor calibration device in accordance with
another embodiment includes a processor configured to apply a
control signal, detect a measured response to the control signal,
determine a variance in the detected measured response, and
estimate a sensor sensitivity based on the variance in the detected
measured response.
[0094] The processor may be configured to vary the level of the
control signal with time.
[0095] In another aspect, the processor may be configured to apply
a square wave signal to a poise voltage.
[0096] The processor in a further aspect may be configured to
determine a work electrode current signal of an analyte sensor
operatively coupled to the processor.
[0097] Moreover, the processor may be configured to determine the
variance based on comparing the difference between the beginning
and end of the half duty cycle of the measured response to the
control signal.
[0098] In addition, the processor in a further aspect may be
configured to retrieve a predetermined sensor sensitivity
corresponding to the determined variance in the detected measured
response.
[0099] The processor may be operatively coupled to a data receiver
unit configured to determine a validity of the estimated sensor
sensitivity, where the data receiver unit may be configured to
determine an analyte level based on the estimated sensor
sensitivity.
[0100] The various processes described above including the
processes performed by the transmitter processor 204 in the
software application execution environment in the transmitter unit
102 including the processes and routines described in conjunction
with FIGS. 4-6 and 9, may be embodied as computer programs
developed using an object oriented language that allows the
modeling of complex systems with modular objects to create
abstractions that are representative of real world, physical
objects and their interrelationships. The software required to
carry out the inventive process, which may be stored in the memory
(not shown) of the transmitter unit 102 may be developed by a
person of ordinary skill in the art and may include one or more
computer program products.
[0101] Various other modifications and alterations in the structure
and method of operation of this invention will be apparent to those
skilled in the art without departing from the scope and spirit of
the invention. Although the invention has been described in
connection with specific preferred embodiments, it should be
understood that the invention as claimed should not be unduly
limited to such specific embodiments. It is intended that the
following claims define the scope of the present invention and that
structures and methods within the scope of these claims and their
equivalents be covered thereby.
* * * * *