Non-invasive method for estimating of the variation of the glucose level in the blood of a person and apparatus for carrying out the method

• US 8,886,274 B2
• Filed: 08/26/2009
• Issued: 11/11/2014
• Est. Priority Date: 08/29/2008
• Status: Active Grant

• Current Assignee: Gerinova AG
• Original Assignee: Gerinova AG
• Inventors: Gericke, Monica, Paramonov, Boris A., Turkovskiy, Ivan Ivanovich
• Primary Examiner(s): D'ANGELO, MICHAEL J
• Application Number:
  US12/737,908
• Publication Number:
  US 20110224521A1
• Time in Patent Office: 1,903 Days
• Field of Search: 600/345, 600/347, 600/365
• US Class Current: 600/345
• CPC Class Codes: A61B 2560/0252 using ambient temperature
• CPC Class Codes: A61B 5/03 Detecting, measuring or recording fluid pressure within the body other than blood pressure, e.g. cerebral pressure; Measuring pressure in body tissues or organs A61B5/205 takes precedence
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/4519 Muscles A61B5/389, A61B5/224 take precedence
• CPC Class Codes: A61B 5/681 Wristwatch-type devices

Abstract

The estimation of the variation of the glucose level in the blood of a person by the variation of the volume of the interstitial fluid compartments in muscular tissue due to a shift of fluid between the extracellular and intracellular compartments caused by variations of the osmotic pressure of the extracellular fluids which is in turn correlated with the glucose level. The variation of the volume of the interstitial fluid compartments is detected by a non-invasive conductometry measurement using electrodes placed in contact with the skin of the person overlying a portion of soft tissue including muscular fibers. To eliminate the adverse effect of the conductivity of the capillary vessels, the conductivity of the tissue is measured independently in two directions, namely parallel and transverse to the muscular fibers.

Claims

1. A noninvasive method for estimating a variation of glucose level Δ

G in the blood of a person within a time interval Δ

t, comprising the following steps;

placing a first tetrapolar electrode device in contact with skin of the person overlying a portion of soft tissue including muscular fibers oriented parallel to the direction of the muscular fibers;

placing a second tetrapolar electrode device in contact with the skin of said person overlying said portion of soft tissue oriented transverse to the direction of the muscular fibers;

measuring for a time interval Δ

t;

with the first tetrapolar electron device a relative variation Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub> of the conductivity value C<sub>∥

,LF</sub> of said tissue parallel to the direction of the muscular fibers at a low frequency;

with the second tetrapolar electron device a relative variation Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> of a conductivity value C<sub>⊥

,LF</sub> of said tissue transverse to the direction of the muscular fibers at said low frequency;

estimating Δ

G by a processing apparatus as;

0.0 if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>≈

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

+a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>>

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

−

a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub><

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

wherein;

a is in the range of 0.15-1.0 μ

M/l sec;

the low frequency is in the range of 1·

×

10⁴ Hz-5·

×

10⁴ Hz; and

“

≈

”

means “

equal within a range of +/−

2.5%-+/−

7.5%”

.

2. The method according to claim 1, wherein Δ

t is in the range of not more than 15 seconds.

3. The method according to claim 1, further comprising the following steps:

measuring for the time interval Δ

t;

with the first tetrapolar electron device a relative variation Δ

C<sub>∥

,HF</sub>/C<sub>∥

,HF</sub> of a conductivity value C<sub>∥

,HF</sub> of said tissue parallel to the direction of the muscular fibers at a high frequency;

with the second tetrapolar electron device the relative variation Δ

C<sub>⊥

,HF</sub>/C<sub>⊥

,HF</sub> of the conductivity value C<sub>⊥

,HF</sub> of said tissue transverse to the direction of the muscular fibers at said high frequency;

estimating Δ

G by a processing apparatus as;

+a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>>

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> and Δ

C<sub>∥

,HF</sub>/C<sub>∥

,HF</sub>≈

Δ

C<sub>⊥

,HF</sub>/C<sub>⊥

,HF</sub>

+b if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>>

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> and Δ

C<sub>∥

,HF</sub>/C<sub>∥

,HF</sub>>

Δ

C<sub>⊥

,HF</sub>/C<sub>⊥

,HF</sub>

−

a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub><

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> and Δ

C<sub>∥

,HF</sub>/C<sub>∥

,HF</sub>≈

Δ

C<sub>⊥

,HF</sub>/C<sub>⊥

,HF</sub>; and

−

b if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub><

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> and Δ

C<sub>∥

,HF</sub>/C<sub>∥

,HF</sub><

Δ

C<sub>⊥

,HF</sub>/C<sub>⊥

,HF</sub>;

wherein;

a is in the range of 0.15-0.5 μ

M/l second;

b is in the range of 0.3-1.0 μ

M/l second; and

the high frequency is in the range of 0.5·

×

10⁶ Hz-5·

×

10⁶ Hz.

4. The method according to claim 1, and further comprising the steps of:

providing a pair of inner electrodes and a pair of outer electrodes to said tetrapolar electrode devices;

applying alternating currents having said low or high frequency to one of the pairs of electrodes of said tetrapolar electrode devices for obtaining impedance values, and

measuring the alternating voltages resulting from such currents at the other one of the pairs of electrodes.

5. The method according to claim 4, wherein the conductivity values C are obtained by calculation from the applied alternating currents and the measured alternating voltages after rectification and digitizing.

6. The method according to claim 1, further comprising the steps of:

placing a temperature sensor in contact with the skin of said person overlying said portion of soft tissue;

measuring the temperature T of the skin; and

correcting the conductivity values by a factor f,

wherein;

f is a reduction factor in case of a temperature decrease;

f is in the range of 4.5-6.5% per °

C. temperature difference from T₀ for the low frequency measurements; and

T₀ is a previously measured temperature of the skin of said person overlying said portion of soft tissue.

7. The method according to claim 6, wherein f is in the range of 1.5-2.5% per °

C. temperature difference from T₀ for the high frequency measurements.

8. The method according to claim 6, wherein the measured temperature T of the skin is digitized and correction of the conductivity values by said factor f is carried out by calculation.

9. The method according to claim 1, wherein the steps of placing the first tetrapolar electrode device in contact with the skin of the person overlying a portion of soft tissue including muscular fibers oriented parallel to the direction of the muscular fibers and placing the second tetrapolar electrode device in contact with the skin of the person overlying said portion of soft tissue oriented transverse to the direction of the muscular fibers include the following steps:

placing eight tetrapolar electron devices in contact with the skin of the person overlying said portion of soft tissue oriented along eight axes forming a radially symmetric scheme;

measuring a conductivity value of said tissue with each one of said eight tetrapolar electron devices to define the axis with minimal conductivity and the axis with maximal conductivity;

using the tetrapolar electrode device oriented along the axis with maximal conductivity as the first tetrapolar electrode device; and

using the tetrapolar electrode device oriented along the axis with minimal conductivity as the second tetrapolar electrode device.

10. An apparatus for estimating a variation of glucose level Δ

G in the blood of a person within a time interval Δ

t, comprising;

a first tetrapolar electrode device in contact with skin of the person overlying a portion of soft tissue including muscular fibers oriented parallel to the direction of the muscular fibers;

a second tetrapolar electrode device in contact with the skin of said person overlying said portion of soft tissue oriented transverse to the direction of the muscular fibers;

a processing apparatus for measuring for a time interval Δ

t;

with the first tetrapolar electron device a relative variation Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub> of the conductivity value C<sub>∥

,LF</sub> of said tissue parallel to the direction of the muscular fibers at a low frequency;

with the second tetrapolar electron device a relative variation Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub> of a conductivity value C<sub>∥

,LF</sub> of said tissue transverse to the direction of the muscular fibers at said low frequency;

estimating AG by the processing apparatus as;

0.0 if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>≈

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

+a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub>>

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

−

a if Δ

C<sub>∥

,LF</sub>/C<sub>∥

,LF</sub><

Δ

C<sub>⊥

,LF</sub>/C<sub>⊥

,LF</sub>

wherein;

a is in the range of 0.15-1.0 μ

M/l sec;

the low frequency is in the range of 1·

×

10⁴ Hz-5·

×

10⁴ Hz; and

“

≈

”

means “

equal within a range of +/−

2.5%-+/−

7.5%”

.

11. The apparatus according to claim 10, further comprising having eight tetrapolar electrode devices oriented along eight axis forming a radially symmetric scheme.

12. The apparatus according to claim 10, further comprising a device for generating alternating currents.

13. The apparatus according to claim 10, further comprising a device for rectifying said alternating currents and measured alternating voltages, for digitizing rectified currents and rectified voltages and for processing digitized data.

14. The apparatus according to claim 13, further comprising a device for transmitting processed data to an external data processing apparatus.

15. The apparatus according to claim 10, further comprising a temperature sensor, wherein the temperature sensor is located in the center of the tetrapolar electrode devices.