Non-invasive monitoring of blood metabolite levels

• US 9,307,935 B2
• Filed: 06/04/2010
• Issued: 04/12/2016
• Est. Priority Date: 10/27/2008
• Status: Active Grant

• Current Assignee: BioSensors, Inc.
• Original Assignee: BioSensors, Inc.
• Inventors: Pluta, Sarah E., Hewitt, John W.
• Primary Examiner(s): Mallari, Patricia
• Assistant Examiner(s): CATINA, MICHAEL ANTHONY
• Application Number:
  US13/377,162
• Publication Number:
  US 20120130212A1
• Time in Patent Office: 2,139 Days
• Field of Search: 600/345, 600/347, 600/365, 600/316
• US Class Current: 1/1
• CPC Class Codes: A61B 2562/0215 Silver or silver chloride containing
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/0531 Measuring skin impedance
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes

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.

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, the threshold being equal to approximately a ten percent difference,

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,

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;

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 sensor array contains a planar array of equally spaced electrodes.

6. 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.

17. 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.

7. 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;

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, until a difference between the transmitted electromagnetic signals and the return electromagnetic impedance readings exceeds a threshold, the threshold being equal to approximately a ten percent difference,

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,

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;

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.

8. The monitoring system of claim 7, further comprising a signal generator for generating electromagnetic signals and transmitting the electromagnetic signals to the sensor array.

9. The monitoring system of claim 8, further comprising a signal analyzer for analyzing the electromagnetic signals and generating the electromagnetic impedance readings.

10. The monitoring system of claim 7, wherein the electromagnetic impedance readings are obtained at a frequency between approximately 10 Hz and 10 MHz.

11. The monitoring system of claim 7, wherein the sensor array contains at least seven sensors.

12. The monitoring system of claim 11, wherein the at least seven sensors are arranged in a substantially linear arrangement.

13. The monitoring system of claim 7, 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.

16. The monitoring system of claim 13, wherein the current transmitting electrode, the current sensing electrode and the two voltage sensing electrodes are spaced equally from one another within the sensor array.

18. The monitoring system of claim 7, 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.

14. A program product 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;

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 within approximately ten minutes, 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 equal to approximately a ten percent difference,

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; and

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.

15. The program product of claim 14, 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.

19. The program product of claim 14, 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.