U.S. patent application number 15/050745 was filed with the patent office on 2016-06-16 for non-invasive monitoring of blood metabolite levels.
The applicant listed for this patent is BioSensors, Inc.. Invention is credited to John W. Hewitt, Sarah E. Pluta.
Application Number | 20160166187 15/050745 |
Document ID | / |
Family ID | 43309416 |
Filed Date | 2016-06-16 |
United States Patent
Application |
20160166187 |
Kind Code |
A1 |
Pluta; Sarah E. ; et
al. |
June 16, 2016 |
NON-INVASIVE MONITORING OF BLOOD METABOLITE LEVELS
Abstract
Solutions for non-invasively monitoring blood metabolite levels
of a patient are disclosed. In one embodiment, the method includes:
repeatedly measuring a plurality of electromagnetic impedance
readings with a sensor array from: an epidermis layer of a patient
and one of a dermis layer or a subcutaneous layer of the patient,
until a difference between the readings exceeds a threshold;
calculating an impedance value representing the difference using an
equivalent circuit model and individual adjustment factor data
representative of a physiological characteristic of the patient;
and determining a blood metabolite level of the patient from the
impedance value and a blood metabolite level algorithm, the blood
metabolite level algorithm including blood metabolite level data
versus electromagnetic impedance data value correspondence of the
patient.
Inventors: |
Pluta; Sarah E.; (Scotia,
NY) ; Hewitt; John W.; (Niskayuna, NY) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BioSensors, Inc. |
Schenectady |
NY |
US |
|
|
Family ID: |
43309416 |
Appl. No.: |
15/050745 |
Filed: |
February 23, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13377162 |
Jan 10, 2012 |
9307935 |
|
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PCT/US2010/037361 |
Jun 4, 2010 |
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15050745 |
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61185258 |
Jun 9, 2009 |
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Current U.S.
Class: |
600/347 ;
600/345 |
Current CPC
Class: |
A61B 5/14532 20130101;
A61B 5/14546 20130101; A61B 5/1495 20130101; A61B 5/0531 20130101;
A61B 2562/046 20130101; A61B 2562/0215 20170801; A61B 5/1468
20130101 |
International
Class: |
A61B 5/145 20060101
A61B005/145; A61B 5/1468 20060101 A61B005/1468; A61B 5/053 20060101
A61B005/053 |
Claims
1. A method of determining a blood metabolite level of a patient,
the method comprising: repeatedly transmitting, using a sensor
array, a plurality of electromagnetic signals into an epidermis
layer of a patient and one of a dermis layer of the patient, or the
dermis layer and a subcutaneous layer of the patient; repeatedly
obtaining a plurality of return electromagnetic impedance readings,
using the sensor array, from: the epidermis layer of a patient and
the one of the dermis layer or the dermis layer and the
subcutaneous layer of the patient, until a difference between the
transmitted electromagnetic signals and the return electromagnetic
impedance readings exceeds a threshold, wherein exceeding the
threshold indicates that the transmitted plurality of
electromagnetic signals penetrated the at least one of the dermis
layer, or the dermis layer and subcutaneous layer; calculating, at
a glucose monitoring system having a processing unit and a memory,
an impedance value representing the difference between the
transmitted electromagnetic signals and the return electromagnetic
signals using an equivalent circuit model and individual adjustment
factor data representative of a physiological characteristic of the
patient; and determining a blood metabolite level of the patient
from the impedance value and a blood metabolite level algorithm,
the blood metabolite level algorithm including blood metabolite
level data versus electromagnetic impedance data value
correspondence.
2. The method of claim 1, further comprising: calibrating the
sensor array based on the determined blood metabolite level of the
patient and a known blood metabolite level of the patient obtained
independently of the determined blood metabolite level of the
patient.
3. The method of claim 1, wherein the blood metabolite level is a
one of a glucose level, an electrolyte level or an analyte
level.
4. The method of claim 1, wherein the individual adjustment factor
data includes information about at least one of: a weight of the
patient, a sex of the patient, a body fat percentage of the
patient, a heart rate of the patient, an age of a patient, and a
race of a patient.
5. The method of claim 1, wherein the threshold is equal to
approximately a ten percent difference between the transmitted
electromagnetic signals and the return electromagnetic impedance
readings.
6. The method of claim 1, wherein the repeatedly transmitting of
the plurality of electromagnetic signals and the repeatedly
obtaining of the plurality of return electromagnetic impedance
readings is performed within approximately ten minutes.
7. The method of claim 1, wherein the sensor array contains a
planar array of equally spaced electrodes.
8. The method of claim 1, wherein the equivalent circuit model
includes an equivalent circuit equation including:
D=((ZK/(ZJ+ZK))-(ZM/(ZM+ZL)) where ZJ is a first electromagnetic
impedance reading from the epidermis layer, ZM is a second
electromagnetic impedance reading from the epidermis layer, ZK is a
first electromagnetic impedance reading from the one of the dermis
layer or the dermis layer and the subcutaneous layer, ZL is a
second electromagnetic impedance reading from the one of the dermis
layer or the dermis layer and the subcutaneous layer, and D is the
impedance value representing the difference.
9. The method of claim 1, wherein in response to determining that
the difference between the transmitted electromagnetic signals and
the return electromagnetic impedance readings does not exceed the
threshold, repeating the transmitting of the plurality of
electromagnetic signals and the obtaining of the plurality of
return electromagnetic impedance readings for approximately ten
minutes, and stopping.
10. A monitoring system for at least one of a glucose level, an
electrolyte level or an analyte level, the monitoring system
comprising: a sensor array for repeatedly transmitting a plurality
of electromagnetic signals into an epidermis layer of a patient and
one of a dermis layer of the patient, or the dermis layer and a
subcutaneous layer of the patient; a comparator for repeatedly
obtaining a plurality of return electromagnetic impedance readings
from: the epidermis layer of a patient and the one of the dermis
layer or the dermis layer and the subcutaneous layer of the
patient, from the sensor array, until a difference between the
transmitted electromagnetic signals and the return electromagnetic
impedance readings exceeds a threshold, wherein exceeding the
threshold indicates that the transmitted plurality of
electromagnetic signals penetrated the at least one of the dermis
layer, or the dermis layer and subcutaneous layer; a calculator for
calculating an impedance value representing the difference between
the transmitted electromagnetic signals and the return
electromagnetic signals using an equivalent circuit model and
individual adjustment factor data representative of a physiological
characteristic of the patient; and a determinator for determining
the at least one of the glucose level, the electrolyte level or the
analyte level of the patient from the impedance value and at least
one of a glucose algorithm, an electrolyte algorithm or an analyte
algorithm.
11. The monitoring system of claim 10, further comprising a signal
generator for generating electromagnetic signals and transmitting
the electromagnetic signals to the sensor array.
12. The monitoring system of claim 11, further comprising a signal
analyzer for analyzing the electromagnetic signals and generating
the electromagnetic impedance readings.
13. The monitoring system of claim 10, wherein the threshold is
equal to approximately a ten percent difference between the
transmitted electromagnetic signals and the return electromagnetic
impedance readings.
14. The monitoring system of claim 10, wherein the repeatedly
transmitting of the plurality of electromagnetic signals and the
repeatedly obtaining of the plurality of return electromagnetic
impedance readings is performed within approximately ten
minutes.
15. The monitoring system of claim 10, wherein the electromagnetic
impedance readings are obtained at a frequency between
approximately 10 Hz and 10 MHz.
16. The monitoring system of claim 10, wherein the sensor array
contains at least seven sensors, wherein the at least seven sensors
are arranged in a substantially linear arrangement.
17. The monitoring system of claim 10, wherein the sensor array
includes a current transmitting electrode, a current sensing
electrode, and two voltage sensing electrodes positioned on the
epidermis layer of the patient in a linear arrangement.
18. The monitoring system of claim 10, wherein in response to
determining that the difference between the transmitted
electromagnetic signals and the return electromagnetic impedance
readings does not exceed the threshold, repeating the transmitting
of the plurality of electromagnetic signals and the obtaining of
the plurality of return electromagnetic impedance readings for
approximately ten minutes, and stopping.
19. A program product comprising program code stored on a
non-transitory computer readable medium, which when executed by a
computer, causes the computer to perform the following: instructs a
sensor array to repeatedly transmit a plurality of electromagnetic
signals into an epidermis layer of a patient and one of a dermis
layer of the patient, or the dermis layer and a subcutaneous layer
of the patient; and determines a blood metabolite level of a
patient based on a plurality of repeatedly obtained return
electromagnetic impedance readings collected from the epidermis
layer of the patient and the one of the dermis layer, or the dermis
layer and the subcutaneous layer of the patient, the plurality of
electromagnetic signals being repeatedly transmitted and the
plurality of return electromagnetic readings being repeatedly
obtained until a difference between the plurality of transmitted
electromagnetic signals and the plurality of obtained return
electromagnetic readings exceeds a threshold, wherein exceeding the
threshold indicates that the transmitted plurality of
electromagnetic signals penetrated the at least one of the dermis
layer, or the dermis layer and subcutaneous layer.
20. The program product of claim 19, wherein the program code, when
executed by the computer, further provides instructions for
calibrating the sensor array based on the determined blood
metabolite level of the patient and a known blood metabolite level
of the patient obtained independently of the determined blood
metabolite level of the patient.
21. The program product of claim 19, wherein the blood metabolite
level is one of a glucose level of the patient, an electrolyte
level of the patient or an analyte level of the patient.
22. The program product of claim 19, wherein the threshold is equal
to approximately a ten percent difference between the transmitted
electromagnetic signals and the return electromagnetic impedance
readings.
23. The program product of claim 19, wherein the repeatedly
transmitting of the plurality of electromagnetic signals and the
repeatedly obtaining of the plurality of return electromagnetic
impedance readings is performed within approximately ten
minutes
24. The program product of claim 19, wherein in response to
determining that the difference between the transmitted
electromagnetic signals and the return electromagnetic impedance
readings does not exceed the threshold, repeating the transmitting
of the plurality of electromagnetic signals and the obtaining of
the plurality of return electromagnetic impedance readings for
approximately ten minutes, and stopping.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is related in part to U.S. utility patent
application Ser. No. 12/258,509, filed on 27 Oct. 2008, and is a
continuation application of U.S. patent application Ser. No.
13/377,162, filed on 9 Jun. 2009, each of which is hereby
incorporated by reference in its entirety.
BACKGROUND
[0002] The present disclosure relates to non-invasive monitoring of
blood metabolite levels of a patient. More specifically, the
present disclosure relates to solutions for non-invasively
monitoring blood metabolite levels of a patient using a sensor
array and electromagnetic impedance tomography.
[0003] Blood metabolite levels, including glucose, lactic acid and
hydration levels, are important indicators of health and the
physical condition of a patient. In non-invasive blood-metabolite
monitoring systems, measurements of biological data are taken at
the surface (epidermis) of a patient's body. These surface
measurements are more sensitive to changes in the body than those
invasive measurements taken at the layers below (e.g., dermis or
subcutaneous layers). Fluctuations in temperature, perspiration,
moisture level, etc., can cause rapid and dramatic variations in a
patient's biological data. When attempting to determine biological
data (i.e., blood metabolite levels) through the epidermis layer
(using sensors on the skin), difficulties arise in compensating for
these variations.
SUMMARY
[0004] Solutions are disclosed that enable non-invasive monitoring
of blood metabolite levels of a patient. In one embodiment, a
method includes repeatedly measuring a plurality of electromagnetic
impedance readings with a sensor array from: an epidermis layer of
a patient and one of a dermis layer or a subcutaneous layer of the
patient, until a difference between the readings exceeds a
threshold; calculating an impedance value representing the
difference using an equivalent circuit model and individual
adjustment factor data representative of a physiological
characteristic of the patient; and determining a blood metabolite
level of the patient from the impedance value and a blood
metabolite level algorithm, the blood metabolite level algorithm
including blood metabolite level data versus electromagnetic
impedance data value correspondence of the patient.
[0005] A first aspect of the invention provides a method
comprising: repeatedly measuring a plurality of electromagnetic
impedance readings with a sensor array from: an epidermis layer of
a patient and one of a dermis layer or a subcutaneous layer of the
patient, until a difference between the readings exceeds a
threshold; calculating an impedance value representing the
difference using an equivalent circuit model and individual
adjustment factor data representative of a physiological
characteristic of the patient; and determining a blood metabolite
level of the patient from the impedance value and a blood
metabolite level algorithm, the blood metabolite level algorithm
including blood metabolite level data versus electromagnetic
impedance data value correspondence of the patient.
[0006] A second aspect of the invention provides a blood metabolite
level monitoring system comprising: a sensor array for repeatedly
measuring a plurality of electromagnetic impedance readings from:
an epidermis layer of a patient and one of a dermis layer or a
subcutaneous layer of the patient, until a difference between the
readings exceeds a threshold; a calculator for calculating an
impedance value representing the difference, the calculator
including an equivalent circuit model and individual adjustment
factor data representative of a physiological characteristic of the
patient; and a determinator for determining a blood metabolite
level of the patient from the impedance value and a blood
metabolite level algorithm.
[0007] A third aspect of the invention provides a program product
stored on a computer readable medium, which when executed, performs
the following: obtains a plurality of electromagnetic impedance
readings about: an epidermis layer of a patient and one of a dermis
layer or a subcutaneous layer of the patient; analyzes the
electromagnetic impedance readings to determine a difference;
calculates an impedance value representing the difference using an
equivalent circuit model and individual adjustment factor data
representative of a physiological characteristic of the patient;
and determines a blood metabolite level of the patient from the
impedance value and a blood metabolite level algorithm, the blood
metabolite level algorithm including blood metabolite level data
versus electromagnetic impedance data value correspondence of the
patient.
[0008] A fourth aspect of the invention provides a blood metabolite
monitoring system comprising: a device that determines a blood
metabolite level of a patient based on a plurality of
electromagnetic impedance readings measured from the patient within
a single blood metabolite cycle of the patient.
[0009] A fifth aspect of the invention provides a method for
monitoring a blood metabolite level of a patient, the method
comprising: determining a blood metabolite level of a patient based
on a plurality of electromagnetic impedance readings measured from
the patient within a single blood metabolite cycle of the
patient.
[0010] A sixth aspect of the invention provides a program product
stored on a computer readable medium, which when executed, performs
the following: determines a blood metabolite level of a patient
based on a plurality of electromagnetic impedance readings
collected from the patient within a single blood metabolite cycle
of the patient.
[0011] A seventh aspect of the invention provides a blood
metabolite monitoring system comprising: a signal generator for
transmitting an electromagnetic signal; a sensor array for:
receiving the electromagnetic signal from the signal generator and
applying the electromagnetic signal to a patient; and
non-invasively measuring a plurality of electromagnetic impedance
readings from: an epidermis layer of the patient and one of a
dermis layer or a subcutaneous layer of the patient; a comparator
for comparing a difference between the plurality of electromagnetic
impedance readings to a threshold; and a controller for controlling
the signal generator and the comparator, the controller providing
instructions for repeating the transmitting, non-invasively
measuring, and comparing in response to the difference being less
than the threshold.
[0012] An eight aspect of the invention provides a program product
stored on a computer readable medium, which when executed, performs
the following: transmits an electromagnetic signal to a sensor
array; receives a plurality of electromagnetic impedance readings
from the sensor array, the electromagnetic impedance readings being
collected from: an epidermis layer of the patient and one of a
dermis layer or a subcutaneous layer of the patient; compares a
difference between the plurality of electromagnetic impedance
readings to a threshold; and provides instructions for repeating
the transmitting, receiving, and comparing in response to the
difference being less than the threshold.
[0013] A ninth aspect of the invention provides a method for
monitoring a blood metabolite level of a patient, the method
comprising: transmitting an electromagnetic signal to a sensor
array; receiving a plurality of electromagnetic impedance readings
from the sensor array, the electromagnetic impedance readings
collected from: an epidermis layer of the patient and one of a
dermis layer or a subcutaneous layer of the patient; comparing a
difference between the plurality of electromagnetic impedance
readings to a threshold; and repeating the transmitting, receiving,
and comparing in response to the difference being less than the
threshold.
[0014] A tenth aspect of the invention provides a method of
determining a blood metabolite level of a patient, the method
including: repeatedly transmitting, using a sensor array, a
plurality of electromagnetic signals into an epidermis layer of a
patient and one of a dermis layer of the patient, or the dermis
layer and a subcutaneous layer of the patient; repeatedly obtaining
a plurality of return electromagnetic impedance readings, using the
sensor array, from: the epidermis layer of a patient and the one of
the dermis layer or the dermis layer and the subcutaneous layer of
the patient, until a difference between the transmitted
electromagnetic signals and the return electromagnetic impedance
readings exceeds a threshold, wherein exceeding the threshold
indicates that the transmitted plurality of electromagnetic signals
penetrated the at least one of the dermis layer, or the dermis
layer and subcutaneous layer; calculating, at a glucose monitoring
system having a processing unit and a memory, an impedance value
representing the difference between the transmitted electromagnetic
signals and the return electromagnetic signals using an equivalent
circuit model and individual adjustment factor data representative
of a physiological characteristic of the patient; and determining a
blood metabolite level of the patient from the impedance value and
a blood metabolite level algorithm, the blood metabolite level
algorithm including blood metabolite level data versus
electromagnetic impedance data value correspondence.
[0015] An eleventh aspect of the invention provides a monitoring
system for at least one of a glucose level, an electrolyte level or
an analyte level, the monitoring system having: a sensor array for
repeatedly transmitting a plurality of electromagnetic signals into
an epidermis layer of a patient and one of a dermis layer of the
patient, or the dermis layer and a subcutaneous layer of the
patient; a comparator for repeatedly obtaining a plurality of
return electromagnetic impedance readings from: the epidermis layer
of a patient and the one of the dermis layer or the dermis layer
and the subcutaneous layer of the patient, from the sensor array,
until a difference between the transmitted electromagnetic signals
and the return electromagnetic impedance readings exceeds a
threshold, wherein exceeding the threshold indicates that the
transmitted plurality of electromagnetic signals penetrated the at
least one of the dermis layer, or the dermis layer and subcutaneous
layer; a calculator for calculating an impedance value representing
the difference between the transmitted electromagnetic signals and
the return electromagnetic signals using an equivalent circuit
model and individual adjustment factor data representative of a
physiological characteristic of the patient; and a determinator for
determining the at least one of the glucose level, the electrolyte
level or the analyte level of the patient from the impedance value
and at least one of a glucose algorithm, an electrolyte algorithm
or an analyte algorithm.
[0016] A twelfth aspect of the invention provides a program product
having program code stored on a non-transitory computer readable
medium, which when executed by a computer, causes the computer to
perform the following: instructs a sensor array to repeatedly
transmit a plurality of electromagnetic signals into an epidermis
layer of a patient and one of a dermis layer of the patient, or the
dermis layer and a subcutaneous layer of the patient; and
determines a blood metabolite level of a patient based on a
plurality of repeatedly obtained return electromagnetic impedance
readings collected from the epidermis layer of the patient and the
one of the dermis layer, or the dermis layer and the subcutaneous
layer of the patient, the plurality of electromagnetic signals
being repeatedly transmitted and the plurality of return
electromagnetic readings being repeatedly obtained until a
difference between the plurality of transmitted electromagnetic
signals and the plurality of obtained return electromagnetic
readings exceeds a threshold, wherein exceeding the threshold
indicates that the transmitted plurality of electromagnetic signals
penetrated the at least one of the dermis layer, or the dermis
layer and subcutaneous layer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] These and other features of this invention will be more
readily understood from the following detailed description of the
various aspects of the invention taken in conjunction with the
accompanying drawings that depict various embodiments of the
invention, in which:
[0018] FIG. 1 shows a block diagram of an illustrative environment
and computer infrastructure for implementing one embodiment of the
invention.
[0019] FIG. 2 shows a flow diagram of steps in monitoring a glucose
level of a patient according to embodiments of the invention.
[0020] FIG. 3 shows an underside view of a glucose monitor
according to one embodiment of the invention.
[0021] FIG. 4 shows an underside view of a glucose monitor
according to another embodiment of the invention.
[0022] FIG. 5 shows a schematic diagram of a glucose monitor
according to embodiments of the invention.
[0023] FIG. 6 shows an underside view of a glucose monitor
according to an alternative embodiment of the invention.
[0024] FIG. 7 shows an equivalent circuit model diagram according
to embodiments of the invention.
[0025] FIG. 8 shows a top view of a glucose monitor according to an
embodiment of the invention.
[0026] FIG. 9 shows a block diagram of an illustrative environment
and computer infrastructure for implementing one embodiment of the
invention.
[0027] FIG. 10 shows a schematic side view of a sensor array
according to an embodiment of the invention.
[0028] FIG. 11 shows a table including test patterns used according
to embodiments of the invention.
[0029] FIG. 12 shows schematic side views of a sensor array
corresponding to the test patterns of FIG. 11.
[0030] FIG. 13 shows a table including electromagnetic impedance
values obtained during testing according to embodiments of the
invention.
[0031] FIG. 14 shows an equivalent circuit model used during
testing according to embodiments of the invention.
[0032] It is noted that the drawings of the invention are not to
scale. The drawings are intended to depict only typical aspects of
the invention, and therefore should not be considered as limiting
the scope of the invention. In the drawings, like numbering
represents like elements between the drawings.
DETAILED DESCRIPTION
[0033] Shown and described herein are solutions for non-invasively
monitoring blood metabolite levels of a patient. It is understood
that blood metabolite level information may be used to determine a
plurality of physical conditions of a patient. While other blood
metabolite levels such as hydration levels and lactic acid levels
may be monitored using the solutions described herein, glucose
levels are used as the primary illustrative example. It is
understood that these solutions may be easily adapted, with undue
experimentation, to monitor hydration levels, lactic acid levels,
etc. of a patient. For example, the glucose monitoring system 106,
glucose determinator 126 and glucose monitor 140 shown in FIG. 1
and described herein, may alternatively be configured to monitor,
i.e., hydration and/or lactic acid levels of a patient.
[0034] Turning to the drawings, FIG. 1 shows an illustrative
environment 100 for monitoring a glucose level of a patient. To
this extent, environment 100 includes a computer infrastructure 102
that can perform the various processes described herein. In
particular, computer infrastructure 102 is shown including a
computing device 104 that comprises a glucose monitoring system
106, which enables computing device 104 to enable monitoring a
glucose level of a patient by performing the steps of the
disclosure.
[0035] Computing device 104 is shown including a memory 112, a
processor unit (PU) 114, an input/output (I/O) interface 116, and a
bus 118. Further, computing device 104 is shown in communication
with a glucose monitor 140 and a storage system 122. In general,
processor unit 114 executes computer program code, such as glucose
monitoring system 106, which is stored in memory 112 and/or storage
system 122. While executing computer program code, processor unit
114 can read and/or write data, such as electromagnetic impedance
readings 144, to/from memory 112, storage system 122, and/or I/O
interface 116. Bus 118 provides a communications link between each
of the components in computing device 104.
[0036] In any event, computing device 104 can comprise any general
purpose computing article of manufacture capable of executing
computer program code installed by a user (e.g., a personal
computer, server, handheld device, etc.). However, it is understood
that computing device 104 and glucose monitoring system 106 are
only representative of various possible equivalent computing
devices that may perform the various process steps of the
invention. To this extent, in other embodiments, computing device
104 can comprise any specific purpose computing article of
manufacture comprising hardware and/or computer program code for
performing specific functions, any computing article of manufacture
that comprises a combination of specific purpose and general
purpose hardware/software, or the like. In each case, the program
code and/or hardware can be created using standard programming and
engineering techniques, respectively.
[0037] Similarly, computer infrastructure 102 is only illustrative
of various types of computer infrastructures for implementing the
invention. For example, in one embodiment, computer infrastructure
102 comprises two or more computing devices (e.g., a server
cluster) that communicate over any type of wired and/or wireless
communications link, such as a network, a shared memory, or the
like, to perform the various process steps of the invention. When
the communications link comprises a network, the network can
comprise any combination of one or more types of networks (e.g.,
the Internet, a wide area network, a local area network, a virtual
private network, etc.). Regardless, communications between the
computing devices may utilize any combination of various types of
transmission techniques.
[0038] As previously mentioned and discussed further below, glucose
monitoring system 106 enables computing infrastructure 102 to
determine a glucose level of a patient. To this extent, glucose
monitoring system 106 is shown including a comparator 110, a
calculator 124, a glucose determinator 126 and optionally, a
calibrator 128. Also shown in FIG. 1 is glucose monitor 140, which
may include a sensor array 142. Sensor array 142 may obtain
electromagnetic impedance readings 144 from a patient, which may
be, for example, a human being. Glucose monitor 140 may transmit
electromagnetic impedance readings 144 to glucose monitoring system
106 and/or storage system 122. Operation of each of these
components is discussed further herein. However, it is understood
that some of the various functions shown in FIG. 1 can be
implemented independently, combined, and/or stored in memory for
one or more separate computing devices that are included in
computer infrastructure 102. Further, it is understood that some of
the systems and/or functionality may not be implemented, or
additional systems and/or functionality may be included as part of
environment 100.
[0039] Turning to FIG. 2, and with continuing reference to FIG. 1,
embodiments of a method for monitoring a glucose level of a patient
will now be described. In step S1, sensor array 142 repeatedly
measures a plurality of electromagnetic impedance readings 144 from
an epidermis layer and one of a dermis or a subcutaneous layer of a
patient until a difference between the readings exceeds a
threshold. Electromagnetic impedance readings 144 may include data
gathered by measuring the impedance (or "complex" impedance) of a
body part of a patient to an electromagnetic signal, such as, for
example, an alternating current signal. Electromagnetic impedance
readings 144 may include impedance spectral data, which may be
obtained by measuring the impedance of a body part of a patient
across a range of frequencies. The range of frequencies may, for
example, be between 100 Hz and 10 MHz. In one embodiment, the range
of frequencies may be between 100 kHz and 10 MHz. It is understood
that frequency ranges may be controlled by, for example, a signal
generator which may send electromagnetic signals to sensor array
142. In this case, signal generator may be a component in glucose
monitoring system 106, glucose monitor 140, or a separate component
altogether. It is further understood that electromagnetic impedance
readings 144 (e.g., potential differences) may be measured by a
signal analyzer. For example, electromagnetic impedance readings
may be measured by an impedance analyzer, which may be a component
in glucose monitoring system 106, glucose monitor 140, or a
separate component altogether.
[0040] Returning to FIG. 2, step S1 may include two parts: 1)
measuring a plurality of electromagnetic impedance readings 144
from an epidermis layer of a patient with sensor array 142; and 2)
measuring a plurality of electromagnetic impedance readings 144
from one of a dermis layer or a subcutaneous layer of the patient
with sensor array 142. It is understood that plurality of
electromagnetic impedance readings 144 from one of a dermis layer
or a subcutaneous layer of the patient necessarily include data
about the epidermis layer of the patient. As all readings 144
described herein are obtained at the surface (epidermis layer) of a
patient's skin, such readings will always include some data about
the epidermis layer. For example, a reading 144 "from" or "about"
the subcutaneous layer of a patient includes electromagnetic
impedance data about the subcutaneous layer, the dermis layer
(above the subcutaneous), and the epidermis layer (above the dermis
layer).
[0041] Sensor array 142 will now be explained with reference to
FIGS. 3-6, which show examples of sensor array 142, 143, 144 having
a plurality of sensors 240, 242, 250. As shown in FIG. 3, sensor
array 142 may include current transmitting sensors 240, 242,
current receiving sensors 240, 242, and voltage sensors 250.
Operation of each of these elements is discussed herein. While
shown and described in several configurations, arrangements of
sensor array 142 and sensors 240, 242, 250 are merely illustrative.
Current transmitting sensors 240, 242, current receiving sensors
240, 242, and voltage sensors 250 may be positioned in sensor array
142 in other arrangements than those shown in FIG. 3. For example,
voltage sensors 250 may, for example, be positioned between current
transmitting sensors 240, 242 and current receiving sensors 240,
242 in a linear arrangement (FIGS. 4-5). However, current
transmitting sensors 240, 242 and current receiving sensors 240,
242 may, for example, be positioned between voltage sensors 250 in
a linear arrangement. Further, sensor array 142 and sensors 240,
242, 250 may, for example, be configured in other arrangements such
as circular or arced arrangements. FIGS. 4-6 show alternative
embodiments of sensor array 142. As shown in FIG. 3, sensor array
142 includes sixteen sensors. However, sensor array 142 may contain
fewer or greater numbers of sensors 240, 242, 250 than those shown.
For example, sensor array 143 of FIG. 4 includes eight sensors 240,
242, 250, while sensor array 144 of FIG. 6 includes ten sensors
240, 242, 250. Sensor array 142 and sensors 240, 242, 250 may be
formed of conductive materials including, for example,
silver/silver chloride, platinum or carbon. However, sensor array
142 and sensors 240, 242, 250 may be formed of other conductive
materials now known or later developed. In one embodiment, sensors
240, 242, 250 may be conventional electrodes capable of performing
the functions described herein.
[0042] In any case, sensors 240, 242, 250 may be functionally
interchanged on sensor array 142. Interchanging of sensors 240,
242, 250 may not require physical removal and replacement of
sensors, but may be performed through reprogramming of sensor array
142 by glucose monitoring system 106. For example, sensor array 142
may be reprogrammed by a user via glucose monitoring system 106, to
change sensor 242 from a current transmitting sensor into a current
receiving sensor. Further, sensor array 142 may be reprogrammed by
a user to change sensor 242 from a current transmitting sensor into
a voltage sensor. This interchangeability will be further explained
with reference to FIGS. 4-6.
[0043] Turning back to FIG. 2, and step S1, sensor array 142 may
repeatedly measure plurality of electromagnetic impedance readings
144 from the epidermis layer and one of the dermis layer or
subcutaneous layer of a patient until a difference between the
readings exceeds a threshold. Plurality of electromagnetic
impedance readings 144 from the epidermis layer may be measured
substantially simultaneously with respect to one another, or may be
measured consecutively. Further, plurality of electromagnetic
impedance readings 144 from one of the dermis layer or subcutaneous
layer may be measured substantially simultaneously with respect to
one another, or may be measured consecutively. Additionally,
plurality of electromagnetic impedance readings 144 from the
epidermis and the dermis or subcutaneous may be measured
substantially simultaneously with respect to one another. In one
embodiment, plurality of electromagnetic impedance readings 144
from the epidermis and one of the dermis or subcutaneous layers may
be measured within less than approximately six minutes of one
another to ensure an accurate measure of the patient's glucose
level. As is known in the art, the typical glucose cycle (cellular
oscillations of glucose metabolism) of a human patient is
approximately two to six minutes long. In some patients, this
glucose cycle may be as long as ten minutes. In this case,
plurality of electromagnetic impedance readings 144 may be measured
within approximately ten minutes of one another. Measuring
plurality of electromagnetic impedance readings 144 within one
glucose cycle of a patient provides an accurate measure of a
glucose level of that patient.
[0044] It is further understood that electromagnetic impedance
readings 144 from the epidermis layer and one of the dermis or
subcutaneous layer are used as "shallow" and "deep" readings,
respectively. As used herein, the epidermis layer refers to the
outer layer of the skin covering the exterior body surface of the
patient. The dermis layer refers to a layer of skin below the
epidermis that includes the papillary dermis and reticular dermis.
The dermis layer also includes small blood vessels (capillary bed)
and specialized cells, including eccrine (sweat) glands and
sebaceous (oil) glands. The subcutaneous layer refers to a layer of
skin beneath the epidermis and dermis layer that includes fatty
tissue and large blood vessels. While the dermis and subcutaneous
layers are described herein with reference to "deep" readings, it
is understood that other layers of tissue below the epidermis may
provide sufficiently "deep" readings as well.
[0045] As described with reference to FIG. 4, sensor array 143 may
pass a plurality of alternating current signals through different
layers of the patient. In one embodiment, a signal generator (not
shown) may generate an electromagnetic signal and transmit that
signal to sensor array 143. In this case, signal generator may be
any conventional signal generator known in the art. In another
embodiment, sensor array 143 may include a signal generator which
produces an electromagnetic signal. In another embodiment, current
transmitting sensor 240 may include, or be electrically coupled to,
a conventional signal generator capable of producing an
electromagnetic signal. In any case, current transmitting sensor
240 and current receiving sensor 242 create an electromagnetic
circuit which uses the layer(s) of the patient as a conducting
medium. As described herein, current transmitting sensor 240 may
produce an alternating current signal which is transmitted through
the layer(s) of the patient, and received by current receiving
sensor 242. The alternating-current signal may be within a
frequency range that maximizes extraction of a glucose reading from
the patient. This frequency may range from about 100 Hz to about 10
MHz. When a signal is transmitted through a layer of the patient, a
voltage differential may be measured within that layer. Voltage
sensors 250 determine this voltage differential within the layer of
the patient, and glucose monitor 140 is capable of transmitting
this voltage differential to glucose monitoring system 106. It is
understood that the number of voltage sensors 250 is merely
illustrative, and that as many as 12 voltage sensors may be located
in sensor array 143 or other sensor arrays 142, 144.
[0046] Turning to FIG. 5, a circuit diagram of glucose monitor 140
having sensor array 143 of FIG. 4 is shown. FIG. 5 includes current
transmitting sensor 240, current receiving sensor 242, and six (6)
voltage sensors 250 (some labels omitted). The alternating current
signal transmitted between current transmitting sensor 240 and
current receiving sensor 242 is indicated by current distribution
lines 270. Equipotential surface lines 272 are also shown,
indicating surfaces of constant scalar potential (voltage).
Further, current measurement line ("I") and voltage measurement
lines "V1", "V2" and "V3" are shown, illustrating that current and
voltages may be measured across sensors 240, 242, 250,
respectively. As shown in FIG. 4, voltage sensors 250 are located
between current transmitting sensors 240, 242 and current receiving
sensors 240, 242 in a linear arrangement. Three "sets" of voltage
sensors 250 are illustrated by voltage measurements V1, V2 and V3.
The relationship between locations of sensors 240, 242, 250, along
with properties of the underlying tissue (or, "material under
test"), dictate the depth at which a voltage may be measured. In
this illustrative example, intersections 280 may demonstrate the
different depths at which a voltage can be measured by showing
where equipotential surface lines 272 intersect current
distribution lines 270. Intersections 280 indicate that voltage
sensors 250 farthest from current transmitting sensor 240 and
current sensing sensor 242 are able to read voltage levels in the
deepest tissue layers. In this case, V1 may represent a voltage
reading across the epidermis layer of a patient. V2 represents a
deeper reading than V1, and may measure data about the dermis layer
of the patient. V3 represents a deeper reading than V2, and may
measure data about the subcutaneous layers of the patient. As is
understood from FIG. 5, interchangeability of sensors 240, 242, 250
may allow for measurements of different tissue layers through
manipulation of sensor types.
[0047] FIG. 6 shows another alternative embodiment of glucose
monitor 140 having sensor array 144. In this embodiment, two
columns, each containing 5 sensors 240, 242, 250 are shown. Each
column may include current transmitting sensor 240, 242, current
receiving sensor 240, 242, and three voltage sensors 250. Voltage
sensors 250 may be located between current transmitting sensor 240,
242 and current receiving sensor 240, 242 in a linear arrangement.
Glucose monitor 140 may measure electromagnetic impedance readings
144 at different layers (i.e., epidermis, dermis, subcutaneous)
using different combinations of voltage sensors 250 within a row or
between columns. As similarly described with reference to FIGS.
3-5, types of sensors 240, 242, 250 in sensor array 144 may be
interchanged within or between columns to allow for measurements of
different tissue layers.
[0048] Returning to FIG. 2, in step S2, comparator 110 compares the
difference between the electromagnetic impedance readings to a
threshold difference. The threshold difference may be, for example,
a single impedance value or an impedance range which establishes
that the difference (in impedance value) contains enough
information about the deep reading to determine a glucose level of
the patient. The threshold difference may be determined by the
location of sensors 240, 242, 250 used to measure electromagnetic
impedance readings, by the signal-to-noise ratio of the electronic
components (not shown) within glucose monitor 140, and by the
characteristics of the material under test (patient tissue). In
order to compensate for fluctuations in electromagnetic impedance
readings 144 from the epidermis layer, the difference must be great
enough to provide sufficient information about the glucose level at
one of the dermis layer or the subcutaneous layer.
[0049] In step S3A, in response to the difference being less than
the threshold difference, the measuring and comparing steps are
repeated until the difference is greater than the threshold
difference. While described herein as a "difference", this value
may be a complex mathematical value and/or a complex equation. The
difference may be calculated using an iterative process of
measuring readings 144 from different layers of a patient and
adjusting subsequent readings 144 based upon known relationships
between layers. For example, in one embodiment, it is unknown if an
initial alternating-current signal will penetrate beyond the
epidermis layer of a patient. In this case, by adjusting locations
of sensors 240, 242, 250 and frequency ranges, different
electromagnetic impedance readings 144 may be obtained. From those
different electromagnetic impedance readings 144 and the known
relationships between a patient's skin layers, penetration of
different layers may be determined. In another embodiment, the
difference may be calculated using one or more mathematical
evaluation techniques such as Nyquist or Neural Networks
techniques. However, it is understood that any other known
mathematical technique may be used as well.
[0050] In step S3, in response to the difference being at least
equal to the threshold difference, calculator 124 calculates an
impedance value representing the difference using an equivalent
circuit model and individual adjustment factor data. The equivalent
circuit model may resemble a traditional alternating current (AC)
bridge circuit equation, whereby impedances of four elements of a
circuit are balanced when a "zero" or null reading is measured at
the output. In this case, the equivalent circuit model uses
plurality of impedance readings 144 from the epidermis layer and
plurality of impedance readings 144 from one of the dermis layer or
subcutaneous layer as "elements" of the AC bridge. FIG. 7 shows an
example of an AC circuit model 300 according to one embodiment of
the invention. In this case, the balancing equation for the
equivalent circuit model may be:
D=((ZK/(ZJ+ZK))-(ZM/(ZL+ZM))
[0051] In the example of FIG. 7, ZJ is a first electromagnetic
impedance reading from the epidermis layer, ZK is a first
electromagnetic impedance reading from the one of the dermis layer
or the subcutaneous layer, ZM is a second electromagnetic impedance
reading from the epidermis layer, ZL is a second electromagnetic
impedance reading from the one of the dermis layer or the
subcutaneous layer, and D is the impedance value representing the
difference. Particular sensors 240, 242, 250 within sensor array
140 used to obtain readings ZJ, ZM, ZK and ZL are chosen by
comparator 110. Using this equation, calculator 124 may calculate
the impedance value representing the difference. It is understood
that the impedance value representing the difference between
readings from the epidermis and one of the dermis or subcutaneous
layers is an impedance value representing one of the dermis or
subcutaneous layers. Therefore, the impedance value D includes
information about the dermis or subcutaneous layer of the patient,
and may be used to determine a glucose level of that patient, as
described herein.
[0052] In step S4, determinator 126 determines a glucose level of
the patient from the impedance value representing the difference
and a glucose algorithm. The glucose algorithm may include
electromagnetic impedance versus glucose level correlation
information. For example, the glucose algorithm may be derived from
empirical data gathered from patients and corresponding
electromagnetic impedance values assigned to that empirical data.
In this case, a plurality of patients may be tested via
conventional glucose-testing techniques, such as the classic
finger-stick approach (further described herein), or other
conventional laboratory testing approach. The glucose-level
determinations made through the conventional test may then be
paired with electromagnetic impedance values and further testing
may be performed to evaluate these pairings. Through this iterative
process, a range of electromagnetic impedances may be correlated to
a range of glucose levels for a particular patient profile. For
example, a patient profile may be established for a group of
patients, with one such example profile being: Caucasian women,
between the ages of 45-50, weighing 120-130 pounds, with 15-18%
body fat, etc. Where a patient falls within this profile, a glucose
level of the patient may be determined using an impedance value
representing the difference between readings (epidermis and
dermis/subcutaneous) measured from the patient, and a glucose
algorithm tailored to the patient's profile. In another embodiment,
the glucose algorithm may be specifically tailored to one patient.
In this case, the glucose algorithm may be derived from empirical
data gathered only from the patient. In contrast to the plurality
of electromagnetic impedance readings gathered in determining a
glucose level of the patient, this empirical data (glucose-level
data and electromagnetic impedance data) may be gathered over a
period lasting longer than one glucose cycle of the patient. This
patient-specific glucose algorithm may provide more accurate
results in determining the patient's glucose level than a glucose
algorithm for a general patient profile. In any case, determinator
126 determines a glucose level of the patient from the impedance
value representing the difference and a glucose algorithm.
[0053] In optional step S5, calibrator 128 may calibrate sensor
array 142 by comparing the glucose level of the patient to a known
glucose level of the patient. The known glucose level of the
patient may be obtained, for example, by a classic finger-stick
approach. In this case, the patient's blood is taken by puncturing
the skin of his/her fingertip, and collecting the blood, for
example, in a vial or other collector. This sample may be tested
with a glucose meter. Blood may also be drawn in a vial, which may
then be analyzed using traditional glucose measuring techniques to
determine a glucose level. A finger-stick is only one example of a
traditional method in which a known glucose level of the patient
may be obtained. A known glucose level of the patient may be
obtained in a variety of other manners known in the art. In any
case, the known glucose level may then be compared to the glucose
level determined by the glucose determinator 126. In the case that
the known glucose level and the determined glucose level are not
the same, calibrator 128 may calibrate glucose monitor 140 by
making adjustments to sensor activity states and types. For
example, in sensor array 143 of FIG. 4, calibrator 128 may provide
instructions to glucose monitor 140 to convert a pair of voltage
sensors 250 into a current transmitting sensor 240 and a current
receiving sensor 242, respectively. Calibrator 128 may further
provide instructions to glucose monitor 140 to use a distinct pair
of voltage sensors 250 for obtaining electromagnetic impedance data
about the patient. Calibration may be performed without a restart
of glucose monitoring system 106, and a calibration queue or wait
time may be indicated on a portion of display 342 (FIG. 8).
[0054] It is understood that calibrating of sensor array 142 may be
performed separately from the steps described herein. For example,
calibrating of sensor array 142 may be performed before the
measuring step S1, and may be based on a patient profile (which may
include data representative of a physiological characteristic of
the patient). This patient profile may include information such as
the patient's body weight, body fat percentage, age, sex, etc. The
patient profile may further include patient-specific information
such as, for example, skin thickness information and testing
location information (e.g., forearm area, wrist, back, etc.). Using
a patient profile, calibrator 128 may provide instructions to
glucose monitor 140 to use one or more voltage sensors and one or
more sets of current transmitting sensors 240 and current receiving
sensors 242 for obtaining electromagnetic impedance data about the
patient.
[0055] Turning to FIG. 8, a top view of glucose monitor 140 is
shown. Glucose monitor 140 may include a display 342, and a
plurality of controls 344. Display 342 may provide a glucose
reading 346 ("Glucose Level: 500 mg/dL"), which is visible to the
patient and others observing display 342. Glucose reading 346 may
be provided in response to actuation of controls 344. In some
cases, glucose reading 346 may include historical glucose data,
which allows a patient to view glucose data over a plurality of
time intervals. Further, glucose reading 346 may provide graphical
representations of glucose data in response to actuation of
controls 344. Additionally, glucose data may be stored and/or
transferred to storage system 122 and/or computer device 104. It
should also be understood that glucose monitor 140 and sensor
arrays 142, 143, 144 may be at separate locations. For example,
sensor arrays 142, 143, 144 may gather electromagnetic impedance
readings 144 from the wrist, back, thigh, etc., of a patient and
transmit electromagnetic impedance readings 144 to glucose monitor
140. Glucose monitor 140 may transmit electromagnetic impedance
readings 144 to, for example, glucose monitoring system 106 using a
hard-wired or wireless connection.
[0056] FIG. 9 shows an illustrative environment 500 for monitoring
a glucose level of a patient according to another embodiment of the
invention. To this extent, environment 500 includes a computer
infrastructure 502 that can perform the various processes described
herein. In particular, computer infrastructure 502 is shown
including a computing device 504 that comprises a glucose
monitoring system 506, which enables computing device 504 to enable
monitoring a glucose level of a patient by performing the steps
described herein. It is understood that as compared with
illustrative environment 100 of FIG. 1, commonly named components
(e.g., memory, calculator, storage system, etc.) may function
similarly as described herein and referenced in FIG. 1.
[0057] As shown in FIG. 9, glucose monitoring system 506 may
include a comparator 510 (optionally), a calculator 524, a glucose
determinator 526 and a calibrator 528 (optionally). Glucose
monitoring system 506 is shown in communication with storage system
522, and/or glucose monitor 540, via computing device 504. Glucose
monitor 540 may include comparator 510 (optionally), a controller
541, a signal generator 543 and a transmitter 546. Glucose monitor
540 is shown in communication with sensor array 542, which may
obtain electromagnetic impedance readings 544 from a patient (not
shown).
[0058] In this embodiment, sensor array 542 may be a separate
component from glucose monitor 540 and glucose monitoring system
506. For example, sensor array 542 may be a disposable array of
electrodes, arranged in any configuration described herein. As
described herein, sensor array 542 may non-invasively obtain
electromagnetic impedance readings 544 from a body part of a
patient. Sensor array 542 may be connected to glucose monitor 540
via hard-wired or wireless means. In any case, sensor array 542 is
capable of exchanging signals with glucose monitor 540 and/or a
patient. In one embodiment, controller 541 may instruct signal
generator 543 to generate an electrical signal (e.g., an
alternating current signal) and transmitter 546 to transmit the
electrical signal to sensor array 542. Signal generator 543 and
transmitter 546 may be any conventional signal generator and
transmitter known in the art. In any case, after sensor array 542
receives the electrical signal from transmitter 546, sensor array
542 may measure a plurality of electromagnetic impedance readings
544 from a patient. Measuring of electromagnetic impedance readings
544 may be performed in any manner described herein or known in the
art. Sensor array 542 may return electromagnetic impedance readings
544 to glucose monitor 540 via any conventional means (e.g.,
separate transmitter located on sensor array 542). However, in the
case that sensor array 542 and glucose monitor 540 are hard-wired
to one another, transmitter 546 and the transmitter located on
sensor array 542 may not be necessary for exchanging electrical
signals. In any case, sensor array 542 may transmit electromagnetic
impedance readings 544 to glucose monitor 540.
[0059] In one embodiment, comparator 510 is a component within
glucose monitor 540. In this case, comparator 510 may function
substantially similarly to comparator 110 of FIG. 1. Upon
instruction from controller 541, comparator 510 compares the
electromagnetic impedance readings 544 to determine if a difference
between the readings 544 exceeds a threshold. If the difference
exceeds the threshold, controller 541 may instruct transmitter 546
to transmit the electromagnetic impedance readings 544 representing
the difference to glucose monitoring system 506. If the difference
does not exceed the threshold, controller 541 may instruct signal
generator 543 and transmitter 546 (optionally) to send additional
electrical signals to sensor array 542 for measuring additional
electromagnetic impedance readings 544. Controller 541 and
comparator 510 may repeat this process until a difference between
the readings 544 exceeds a threshold difference.
[0060] Glucose monitor 540 and glucose monitoring system 506 may be
connected by hard-wired or wireless means. In one embodiment, where
glucose monitor 540 is wirelessly connected to glucose monitoring
system 506, transmitter 546 may transmit electromagnetic impedance
readings 544 to glucose monitoring system 506 using radio frequency
(RF) wireless transmission. In any case, glucose monitor 540
transmits electromagnetic impedance readings 544 to glucose
monitoring system 506, which may function substantially similarly
to glucose monitoring system 106 of FIG. 1.
[0061] In an alternative embodiment, comparator 510 may be a
component in glucose monitoring system 506 (similarly shown and
described with respect to glucose monitoring system 106 of FIG. 1).
In this case, comparator 510 may communicate with glucose monitor
540, and specifically, with controller 541, in order to obtain
electromagnetic impedance readings 544 that represent a threshold
difference. Once obtained, these readings 544 may be processed as
described with reference to FIG. 1 (e.g., using calculator 524,
glucose determinator 526, etc.).
[0062] In another alternative embodiment (shown in phantom),
glucose monitor 540 and its components may be incorporated into
glucose monitoring system 506 (and/or computing device 504). In
this case, illustrative environment 500 includes two components:
computing device 504 and sensor array 542. Here, computing device
504 may be either hard-wired or wirelessly connected to sensor
array 542, and the functions of glucose monitor 540 may all be
performed by glucose monitoring system 506. In any case, glucose
monitoring system 506, glucose monitor 540 and sensor array 542
provide for non-invasive monitoring of a patient's blood metabolite
(e.g., glucose) level.
EXAMPLES
[0063] The following provides particular examples of embodiments
described herein.
Example 1
Identification of Tissue Layers
[0064] The following is an illustrative example of experimental
results obtained through the use of glucose monitor 140 having
sensor array 143 of FIG. 4. All sensors used in this experiment
were disposable BIOPAC.RTM. electrodes (BIOPAC 8 is a registered
trademark of BIOPAC Systems Inc., Goleta, Ca), each electrode
having a diameter of 10.5 mm. FIG. 10 shows a schematic side-view
of sensor array 143, as used in this experiment. As described
herein, each electrode in sensor array 143 was assigned a number
(1-8). Sensor array 143 was configured such that the distance
between electrodes (center-to-center) was X and the distance from
the center of electrode 1 to the center of electrode 8 was 7X
(equal spacing between electrodes). In this example, measurements
were obtained using sets of four electrodes, including one current
transmitting electrode, one current receiving electrode and two
voltage sensing electrodes. FIG. 11 shows a table illustrating nine
test patterns (A through I), used during the experiment. As
illustrated in FIG. 11, entry "A" denotes a current transmitting
electrode, entry "B" denotes a current receiving electrode, and
entries "M" and "N" denote voltage sensing electrodes. It is
understood that current transmitting electrode "A" may be
interchanged with current receiving electrode "B" in all
configurations. As such, for the purposes of this explanation, both
current transmitting electrode "A" and current receiving electrode
"B" will be referred to as "current carrying electrodes A and
B."
[0065] This experiment was performed on a layer of animal skin
tissue and a plurality of layers of animal muscle tissue.
Initially, the animal skin tissue was placed over the plurality of
layers of animal muscle tissue and subjected to an electrical
current. At differing points during this experiment, the animal
skin tissue was placed between animal muscle tissue layers to
determine depth of measurement. An Agilent HP 4192A Impedance
Analyzer ("impedance analyzer") was used to measure the potential
difference between the two voltage sensing electrodes (M and N)
while the electrical current was transmitted between current
carrying electrodes A and B. For the purposes of this experiment, a
limited number of electrode patterns were selected. As such, two
conditions were set: 1) current carrying electrodes A and B were to
be outside voltage detecting electrodes M and N; and 2) the
distance between electrodes A and M were to be equal to the
distance between electrodes N and B in every configuration. Given
these conditions nine possible patterns (A through I) were used
(FIG. 11). Using the impedance analyzer at a frequency of 100 kHz,
electromagnetic impedance data was collected with each electrode
pattern (A through I) for each configuration of skin tissue and
muscle tissue. These tests indicated that the depth at which a
measurement may be obtained depends on the resistivity (i.e.,
1/conductivity) of the material under test (i.e., skin tissue) as
well as the configuration of the four active electrodes used to
complete the measurement. It is known that when the distance
between all electrodes (A, B, M, and N) is equal, the depth of
measurement is equal to the distance between electrodes. Using the
sensor array 143 of FIG. 4, there are two instances when
D(A-M)=D(N-B)=D(M-N). This occurs in patterns A and E of FIG. 10.
In pattern A, D(A-M)=D(N-B)=D(M-N)=11.75 mm and in pattern E,
D(A-M)=D(N-B)=D(M-N)=23.5 mm. Using this theory, electrode pattern
A would determine characteristics of tissue at a depth of 11.75 mm
and electrode pattern E would determine characteristics of tissue
at a depth of 23.5 mm. However, conducting this experiment using
patterns A and E obtained slightly different results. Electrode
pattern A was able to measure a depth of 9.5 mm, while electrode
pattern E was able to measure a depth of 18.75 mm. These are 19%
and 20% deviations, respectively. These deviations were later used
to calibrate sensor array 143 and determine different measurement
depths based upon the material under test and the electrodes used
in sensor array 143.
Example 2
Tissue Volume Removal
[0066] FIG. 12 shows a conceptual model of the measured tissue
volumes and their measured impedances. In this model, Z.sub.A
represents the impedance measurement and volume measured of pattern
A and Z.sub.E represents the impedance measurement and volume
measured of pattern E. In this test, the distance between
electrodes in pattern E is twice that the distance between
electrodes in pattern A (2X versus X). Therefore, when removing the
effect of Z.sub.A from Z.sub.E (determining the difference between
Z.sub.A and Z.sub.E), Z1 is equal to Z.sub.A in series with
Z.sub.A, thus Z1=Z.sub.A Z.sub.A (Equation 1 below). Z.sub.E is the
parallel combination of Z1 and Z2, whereby the parallel combination
equation is, Z.sub.E=(Z1Z2)/(Z1+Z2). Substituting for Z1 results
in, Z.sub.E=(Z.sub.A Z.sub.A)*Z2/((Z.sub.A+Z.sub.A)+Z2), where Z1
is the impedance value of the tissue from the surface to a depth of
X and Z2 is the impedance value of the tissue from a depth of X to
a depth of 2X. In one test, X was equal to approximately 11.75
millimeters (mm). As the goal of the tissue volume removal was to
remove the effect of Z1 from Z.sub.E, Equation 2 was derived from
the equation for Z.sub.E (above), solving for Z2.
Z 1 = Z A + Z A ( Equation 1 ) Z 2 = Z 1 Z E Z 1 - Z E ( Equation 2
) ##EQU00001##
[0067] To confirm the model, a second test was performed, this time
concentrating on patterns A and E and using only animal muscle
tissue having an average thickness of 24.61 mm. Z.sub.A and Z.sub.E
were measured and Z1 and Z2 were calculated using Equations 1 and 2
described above. These magnitude and phase values are displayed in
the table of FIG. 13. These magnitude and phase values help
characterize results when only measuring muscle tissue. As shown in
FIG. 13, the muscle tissue limits are: Z1=1800 and 0.03.degree.,
Z2=4370 and -1.03.degree.. Therefore, when Z1 and Z2 are greater
than 1800 and 4370, respectively, a combination of skin and muscle
are being measured. As Z1 and Z2 approached these limits, it was
understood that Z1 and Z2 were not able to differentiate between
muscle and skin tissue.
Example 3
Tissue Volume Differentiation
[0068] Further tests were performed to determine differences
between readings from the epidermis layer and one of a dermis or
subcutaneous layer of a patient. Using sensor array 143,
electromagnetic impedance readings were measured from a standard
sodium chloride solution of 140 mmol/L. Given a homogenous volume
of sodium chloride solution, the relationships between the volumes
measured by various electrode pairs (FIG. 11) at a single frequency
were empirically derived, whereby:
Z.sub.I=k.sub.IGZ.sub.G=k.sub.ICZ.sub.C (Equation 3)
Z.sub.G=k.sub.GCZ.sub.C (Equation 4)
[0069] Where Z is the impedance of the patterns measured (I, G, C)
and k.sub.IG, k.sub.IC and k.sub.GC were calculated using the
standard sodium chloride solution of 140 mmol/L. To test whether
these empirically derived relationships hold true for animal
tissues, two tests were completed. Test A was conducted on animal
muscle tissue having a thickness of 35 mm, where the k values of
the homogenous muscle tissue were consistent with the sodium
chloride test (above). Test B was conducted with a 1.35 mm thick
piece of animal skin tissue placed over the same animal muscle
tissue as Test A. Using Equation 3, the impedance Z.sub.I was
"distinct" from impedances Z.sub.G and Z.sub.C. Using Equation 4,
the impedance Z.sub.G was not "distinct" from impedance Z.sub.C.
Electromagnetic impedances (Z) were considered "distinct" if the
difference in measured electromagnetic impedances was greater than
10%. The measured electromagnetic impedance magnitude differences
in Test B were:
[0070] 1) Percent difference between Z.sub.I and
Z.sub.G.about.29%,
[0071] 2) Percent difference between Z.sub.I and Z.sub.C.about.37%,
and
[0072] 3) Percent difference between Z.sub.G and
Z.sub.C.about.7%.
Example 4
Tissue Volume Differentiation and Removal (VDR)
[0073] After determining that tissue volume differentiation and
tissue volume removal were separately possible, it is possible to
conduct volume differentiation and removal (VDR). This approach
included measuring four electromagnetic impedance readings for each
VDR approach. Specifically, two electromagnetic impedance readings
may be measured from the upper volume (i.e., epidermis), while two
electromagnetic impedance readings may be measured from the lower
volume (i.e., dermis or subcutaneous). After identification of
different tissue volumes, detailed above, four measurements may be
used in an equivalent circuit model to calculate electromagnetic
impedance values representing the difference between the volumes.
In one embodiment, two of the four measurements are from the
shallow volume (animal skin tissue), and another two are from the
deep volume (animal skin tissue & animal muscle tissue). The
equivalent circuit model is shown in FIG. 14, and resembles a
traditional alternating current (AC) bridge model, whereby
impedances are "balanced" across a zero or null reading (D). In
FIG. 14, according to one embodiment, the electromagnetic
impedances Z.sub.J, Z.sub.M represent the shallow volume (animal
skin tissue) and the electromagnetic impedances Z.sub.K, Z.sub.L
represent the total volume (i.e., shallow/deep volumes). From the
AC bridge model, the following equivalent circuit model equation
was derived:
D = Zk Zj + Zk = Zm Zl + Zm ( Equation 5 ) ##EQU00002##
[0074] Where "D" is the electromagnetic impedance value
representing the difference between the shallow volume and the deep
volume. By setting D to a zero value and measuring the
electromagnetic impedance of the shallow volume and deep volume,
ratios between the impedance values were determined. In another
embodiment, ZJ, ZK, ZL and ZM may each represent electromagnetic
impedances from more than one volume. For example, ZJ may represent
electromagnetic impedance data about an epidermis layer and a
dermis layer of a patient, while ZK may represent electromagnetic
impedance data about the dermis layer and the epidermis layer of
the patient. In this case, further differentiation between
impedance readings (ZJ, ZK) is necessary to determine the
difference D. In this case, impedance values ZJ and ZK can be
divided into component parts (i.e., real and imaginary parts) and
differentiation may be performed.
[0075] In another case, assumptions may be made about impedance
values and their relationships to one another in order to
facilitate determining the difference D. Looking at FIGS. 12-13,
assumptions may be made about Z2, ZJ, and ZK in order to simplify
determining the difference D. In this case, Z2 represents the
difference D, while ZJ and ZK each represent some algebraic
combination of ZA and ZE. Mathematically, these assumptions are as
follows: D=Z2 (FIG. 11); ZJ=ZM; and ZK=ZL. Using these assumptions
and substituting into Equation 5 results in:
Z2=((Z1*ZE)/(Z1ZE)); and
ZK=ZJ*(Z1*ZE+Z1ZE)/(Z1ZE Z1*ZE).
[0076] While further modifications (assumptions and/or
substitutions) are necessary in order to solve for ZK in the
preceding equation, those modifications are within the level of
skill of one in the art.
[0077] While shown and described herein as a method and system for
monitoring blood metabolite levels (and more specifically, glucose
levels) of a patient, it is understood that the disclosure further
provides various alternative embodiments. That is, the disclosure
can take the form of an entirely hardware embodiment, an entirely
software embodiment or an embodiment containing both hardware and
software elements. In a preferred embodiment, the disclosure is
implemented in software, which includes but is not limited to
firmware, resident software, microcode, etc. In one embodiment, the
disclosure can take the form of a computer program product
accessible from a computer-usable or computer-readable medium
providing program code for use by or in connection with a computer
or any instruction execution system, which when executed, enables a
computer infrastructure to determine a glucose level of a patient.
For the purposes of this description, a computer-usable or computer
readable medium can be any apparatus that can contain, store or
transport the program for use by or in connection with the
instruction execution system, apparatus, or device. The medium can
be an electronic, magnetic, optical, electromagnetic, infrared, or
semiconductor system (or apparatus or device). Examples of a
computer-readable medium include a semiconductor or solid state
memory, such as storage system 122, magnetic tape, a removable
computer diskette, a random access memory (RAM), a read-only memory
(ROM), a tape, a rigid magnetic disk and an optical disk. Current
examples of optical disks include compact disk-read only memory
(CD-ROM), compact disk-read/write (CD-R/W) and DVD.
[0078] A data processing system suitable for storing and/or
executing program code will include at least one processing unit
114 coupled directly or indirectly to memory elements through a
system bus 118. The memory elements can include local memory, e.g.,
memory 112, employed during actual execution of the program code,
bulk storage (e.g., storage system 122), and cache memories which
provide temporary storage of at least some program code in order to
reduce the number of times code must be retrieved from bulk storage
during execution.
[0079] In another embodiment, the disclosure provides a method of
generating a system for monitoring a glucose level of a patient. In
this case, a computer infrastructure, such as computer
infrastructure 102, 502 (FIGS. 1, 9), can be obtained (e.g.,
created, maintained, having made available to, etc.) and one or
more systems for performing the process described herein can be
obtained (e.g., created, purchased, used, modified, etc.) and
deployed to the computer infrastructure. To this extent, the
deployment of each system can comprise one or more of: (1)
installing program code on a computing device, such as computing
device 104, 504 (FIGS. 1, 9), from a computer-readable medium; (2)
adding one or more computing devices to the computer
infrastructure; and (3) incorporating and/or modifying one or more
existing systems of the computer infrastructure, to enable the
computer infrastructure to perform the process steps of the
disclosure.
[0080] In still another embodiment, the disclosure provides a
business method that performs the process described herein on a
subscription, advertising, and/or fee basis. That is, a service
provider, such as an application service provider, could offer to
determine a glucose level of an animal as described herein. In this
case, the service provider can manage (e.g., create, maintain,
support, etc.) a computer infrastructure, such as computer
infrastructure 102, 502 (FIGS. 1, 9), that performs the process
described herein for one or more customers. In return, the service
provider can receive payment from the customer(s) under a
subscription and/or fee agreement, receive payment from the sale of
advertising to one or more third parties, and/or the like.
[0081] As used herein, it is understood that the terms "program
code" and "computer program code" are synonymous and mean any
expression, in any language, code or notation, of a set of
instructions that cause a computing device having an information
processing capability to perform a particular function either
directly or after any combination of the following: (a) conversion
to another language, code or notation; (b) reproduction in a
different material form; and/or (c) decompression. To this extent,
program code can be embodied as one or more types of program
products, such as an application/software program, component
software/a library of functions, an operating system, a basic I/O
system/driver for a particular computing and/or I/O device, and the
like.
[0082] The foregoing description of various aspects of the
invention has been presented for purposes of illustration and
description. It is not intended to be exhaustive or to limit the
invention to the precise form disclosed, and obviously, many
modifications and variations are possible. Such modifications and
variations that may be apparent to a person skilled in the art are
intended to be included within the scope of the invention as
defined by the accompanying claims.
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