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RF Assisted Non Invasive Method For Blood Glucose Monitoring – A Feasibility Study

Jayakrishnan M.P, Sruthy Skaria, Divya Sathyanath and Prof. P. MohananCentre for Research in Electromagnetics and Antennas

Department of ElectronicsCochin University of Science and Technology, Cochin -682022, Kerala.

[email protected]

1Centre for Research in Electromagnetics and Antennas, Dept. of Electronics, CUSAT, Cochin, Kerala

Forum for Electromagnetic Research Methods and Application Technologies (FERMAT)

Acknowledgements


• Board of Research in Nuclear Sciences, Department of Atomic Energy, Govt. of India.

• The Centre for Materials for Electronics Technology (C-MET), Govt. of India.

Copyright


©The use of this work is restricted solely foracademic purposes. The author of this workowns the copyright and no reproduction inany form is permitted without writtenpermission by the author.

Abstract


An RF assisted biosensor for real time blood glucose monitoring inhumans/animals is demonstrated utilizing the resonancecharacteristics of a Complimentary Stepped Impedance Resonator(CSIR). The resonator is excited using the reactive near field of anopen circuit terminated microstrip transmission line. The proposedsensor is found to show linear variation from 0 to 3000mg/dl ofglucose concentration in water. Experiments are carried out usinganimal tissues to confirm the feasibility as an implantable device.

Keywords: Bioimplants, Biosensor, CSIR.

Biography


M.P. Jayakrishnan received the B.Sc. degree inElectronics from the Mahatma Gandhi University,Kottayam, India, and M.Sc. degree in Electronics Sciencefrom the Cochin University of Science and Technology,Kochi, India, in 2012 and 2014, respectively. He iscurrently working towards Ph.D. degree in MicrowaveElectronics at the Cochin University of Science andTechnology (CUSAT), Kochi, India.His research interests include Microwave based Bio-Sensors, Implantable Antennas, Frequency Selectivesurfaces, Metamaterials etc.

CONTENTS


Introduction

Blood Glucose

Need for Blood Glucose Monitoring

Available Methods

Methodology

Measurement Results

Discussions and Future Plans

Centre for Research in Electromagnetics and Antennas, Dept. of Electronics, CUSAT,

Cochin, Kerala7

Facts about Diabetes

Estimated 7% of the population have DiabetesA leading cause of death and disabilityThere is no cure for diabetes till date.

Blood Glucose


The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal.

• Primary Source of Energy

• Stored in form of Lipids with the help of Insulin

• Insulin provides the key for the Glucose to enter a cell and energise

• Absence of Insulin glucose cannot enter the cell

Blood Glucose Regulation


• The process by which the levels of blood sugar, primarilyglucose, are maintained by the body

• Keeps the body in homeostasis

Blood Glucose Regulation


Centre for Research in Electromagnetics and Antennas, Dept. of Electronics, CUSAT, Cochin, Kerala 11

Glycemic control


• The Blood glucose level in humans is measured in mg/dLor mmol/L

• Normal Values are : 79.2 to 110 mg/dL (4.4 to 6.1 mmol/L)

• Hyperglycemia : excessive amount of Glucose in the blood (>200mg/dL): Diabetes Mellitus

• Hypoglycemia : fall in the Blood Glucose level(< 70mg/dL)

Disorders


Symptoms of Glycemic disorder in human body

Abnormal Glucose level will cause…


Shakiness, anxiety, nervousness, Palpitations, tachycardia, Sweating, feeling of warmth(sympathetic muscarinic rather than adrenergic), Pallor, coldness, clamminess, Dilated pupils(mydriasis), Hunger, borborygmus, Nausea, vomiting, abdominal discomfort,

Headache, abdominal discomfort, Headache, Abnormal thinking, impaired

judgment, Nonspecific dysphoria, moodiness, depression, crying, exaggerated concerns,Feeling of numbness, pins and needles (paresthesia), Negativism, irritability, belligerence,combativeness, rage, Personality change, emotional liability, Fatigue, weakness,apathy, lethargy, daydreaming, sleep disorder, Confusion, memory loss, light-headedness ordizziness, delirium, Staring, glassy look, blurred vision, double vision, Flashes of light inthe field of vision, Automatic behaviour, also known as automatism, Difficulty speaking, slurred

speech, Ataxia, incoordination, sometimes mistaken for drunkenness, Focal orgeneral motor deficit, paralysis, hemiparesis, Stupor, coma, abnormal breathing,

Generalized or focal seizures, Blindness.

Methods for Blood Glucose Monitoring


Invasive MethodsChemical Methods

1. Folin-Wu method2. Benedict's method3. Nelson–Somogyi method4. Neocuproine method5. Shaeffer–Hartmann–Somogyi

Enzymatic Methods1. Saifer–Gerstenfeld method2. Trinder method3. Kodak Ektachem4. Glucometer

Non – Invasive Methods1. Near-infrared spectroscopy2. Ultrasound3. Dielectric spectroscopy4. Fluorescent glucose biosensor5. RF- Based Methods

Microwave Engineering & Technology

Electromagnetic waves in the range 300MHz – 30GHz, find applications from Kitchen to Space


Then why not for‘Bio-Sensing’ ?.


Cochin, Kerala17

Current Monitoring Methods

• Common External Methods-Glucose levels are monitored periodically

(Min 2-4 times daily)

-Blood samples are required for most devices.-New testing strips must be used for each reading.

• New Internal Methods-Medtronic Guardian® REAL-Time Continuous Monitor-Continuous Glucose Monitoring (72 hours Max)

-5min intervals nearly 300 readings per day-Internal memory stores results-Used to identify patterns in glucose level variations



Enzymatic Method using Glucose Oxidase (GOx)

The Glucose levels are estimated using theColorimetric or Amperometric analysis ofthe obtained end products



Glucometer

Uses Enzyme (Generally GOx) coated test strips which are analysed Amperometrically, to measure the Blood Glucose Level.

RF-Based Methods


• Backscatter Analysis• Transmission Based Methods• Impedance Analysis• Resonator Based Bio-Sensors


Cochin, Kerala21

Electromagnetic sensing of glucose level

• The biological tissue has distinct dispersive nature

Dispersion regions of an ideal biological tissue (Martinsen, Grimnes, & Schwan, 2002)

Microwave region corresponds to β and δ regions

RF-Based Methods


• Backscatter Analysis

Here the backscattered energy from the human body is analysed in timedomain or frequency domain to get the bulk dielectric constant.

The glucose level is then derived using adequate signal processing.

RF-Based Methods


• Transmission Based Method

The transmission characteristics of the tissues are analysed to find out theglucose level.

RF-Based Methods


• Impedance Analysis

The Glucose levels are obtained from the analysis of the impedancecharacteristics of the tissues.

RF-Based Methods


• Resonator Based Bio-Sensors

Resonator Based Bio-Sensors


Higher Q – Factor

Less interaction with lossy tissues

Higher accuracy as the sample under test is of lesser quantity

Ease of signal processing and interpretation

Near Field sensing is utilized, hence reduced number of uncertainties

Focus of the Study

Feasibility analysis of planar microwave resonators, fornon/minimally invasive blood glucose monitoring system,based on observing the change in resonance frequency ofthe resonators which is a function of their geometry and thedielectric constant of the surrounding medium.


Supporting Evidences for the Proposed Idea

Blood Glucose is stored in the human body in form of lipids and thechemical properties of the lipids change as the glucose concentrationvaries, this property change is reflected as change in the dielectricconstant of blood.


Supporting Evidences for the Proposed Idea


Variation of Blood Glucose : 30 mg/dl and 400 mg/dl Variation of sodium level : 310 mg/dl to 333 mg/dl Variation of chloride level : 337mg/dl to 372 mg/dl

Other minerals : magnesium: 1.8-3.4 mg/dl, calcium: 8.5-10.5 mg/dl, potassium: 13.6-21.4 mg/dl

These values justify that the major contribution to thedielectric constant variation in human blood is due to Glucoselevels

REF : Erdem Topsakal, Tutku Karacolak, and Elaine C. Moreland, “Glucose-Dependent Dielectric Properties of Blood P lasma”, 978-1-4244-6051-9 , IEEE , 2011

Variation in the Dielectric Properties of Blood with Glucose Concentration


REF : Anas Mazady “Non-invasive Glucose Meter”, Electrical and Computer Engineering Department, The University of Connecticut, Storrs, CT 06269-2157


• Loss Tangent of Human Body• Bio Compatibility• Resolution

Perfect impedance matching occurs when •εr1=εr2•σ2 = 0•2π/λg2 * R is large

εr2

εr1

Choice of Resonators


• The Split Ring Resonator (SRR) and its complimentary structure (CSRR)

• The Stepped Impedance Resonator (SIR) and its Complimentary (CSIR)

Two well known high Q sub-wavelength resonators are used for the study

Complimentary Split Ring Resonator (CSRR)

34

Substrate used - Rogers RT/Duroid 5880 Relative permittivity - 2.2Height (h) - 0.8mm External radius (rex) - 5mm Width of rings (w) - 0.4mm Gap between the rings (d) - 0.4mmOperating Frequency - 2.700 GHz.

The Fabricated CSRR structure

Centre for Research in Electromagnetics and Antennas, Dept. of Electronics, CUSAT, Cochin, Kerala

Theoretical Analysis

The Equivalent Circuit and the characteristic expression of SRR.


REF :Anju Pradeep, S. Mridula and P.Mohanan, “Design of an Edge-Coupled Dual- Ring Split-Ring Resonator”, Antennas and Propagation Magazine, IEEE Volume: 53, Page(s): 45 – 54, 2011.

Stepped Impedance Resonator


The Stepped Impedance Resonator (SIR) is a transmission lineloaded with lumped impedances.

Basic Structure of SIR. (a) K<1 and (b) K>1.

K = Impedance Ratioα = Length Ratio

Microstrip version of SIR



𝐾𝐾. cot 12α .𝜃𝜃𝑡𝑡 = tan 1

21 −α .𝜃𝜃𝑡𝑡

𝐾𝐾. cot 12α .𝜃𝜃𝑡𝑡 = −cot 1

21 −α .𝜃𝜃𝑡𝑡

Resonant conditions of an SIRfor odd mode ( fundamental, 2nd harmonic, etc.)

for even mode ( 1st harmonic, 3rd harmonic, etc.)

Electric field distribution in SIR at fundamental mode

Odd mode : There is a voltage (E field) null along the symmetrical plane A-A’

Surface current distribution in SIR at first harmonic mode

Even mode : There is no current flow through the symmetrical plane A-A'



Resonant modes of SIR can be independently controlled by either varying K or α

Relationship between Length Ratio (α) and fs1/f0for different Impedance Ratio (K)


With different α values

Variations in the Fundamental mode and 1st harmonic mode


With different K values

Variations in the Fundamental mode and 1st harmonic mode

CSIR


Design and Optimized Dimensions

The Fabricated CSIR

The Complimentary Stepped Impedance Resonator (CSIR) used forthe study is a complimentary structure derived from a quarter wave-length planar microstrip Stepped Impedance Resonator.

Condition for resonance of quarter wave SIR

Preliminary Work Done


Monostatic antenna setup used for the measurement of backscattered energy from the resonator.

Measurement Results (CSRR)


Cross Section View of CSRR sensor

Measurement Results (CSIR)


Cross Section View of CSIR sensor

Conclusion (Backscatter Analysis)

45

The backscatter analysis technique shows that the resonators distinguish between fluids with different dielectric constant and animal tissues

The drawbacks of the method are

Difficulty in maintaining a constant volume of sample under test

Uncertainty due to arrangement (Space, orientation of the resonator, ambient interference etc...)

Lesser magnitude of response to fluids of dispersive nature, like water, hydrogen peroxide etc..


Proximity Excitation Techniques

46

The resonators are excited using the near field of a 50 Ohms Microstrip transmission line.


The Experimental Setup


The concentration of the glucose is varied from 0 to 3000mg/dlproviding enough settling time for a homogenous concentration. Thechange in resonance frequency of the resonator is observed using theZVB20 PNA, with a frequency span of 10MHz to 3GHz and 6096measurement points.

Measurement Results


Response of the proximity fed CSRR to Glucose concentration

Measurement Results


Response of the proximity fed CSIR to Glucose concentration

Measurement Results (contd….)


Response to Animal Tissues3mm thick layers ofblood drained fleshand skin tissues of abovine animal areused for the analysis

BiologicalTissue (Bovine)

Relative Permittivity

Loss Tangent

Muscle Tissues 52 0.33Skin Tissues(Wet) 17-30 0.24

Blood 58 0.27REF : Camelia Gabriel, “Compilation of the dielectric properties of body Tissues at RF and microwave frequencies”, Physics Department, King'sCollege London, London WC2R 2LS, UK., 1996



Response of proximity fed CSRR



Response of proximity fed CSIR

Discussions and Future Plans


• The proposed study proves the concept of using CSIR asan efficient biosensor for blood glucose monitoring

Future Plans

• Labelling• Bio – compatibility• Calibration• SAR Studies

References


1. Lt. Gen. A.R. Metha, et. al. “ Diabetes Mellitus in India: The Modern Scourge”, MedicalJournal Armed Forces India, Volume 65 – 2009, India

2. Cynthia M. Ripsin, et. al. “Managament of Blood Glucose in Type 2 Diabetes Mellitus”.American Family Physician , Volume 70, January 2009.

3. F. Falcone, et al. “Babinet Principle Applied to the Design of Metasurfaces andMetamaterials” Physical Review Letters Volume 93, Number 19. The American PhysicalSociety 2004

4. M.Makimoto and Y.Yamashita, “Microwave Resonators and Filters for Wirelesscommunication, Theory Design and Application”, Springer series in AdvancedMicroelectronics, vol.4, 1994.

5. Kurt Fenske and Devendra Misra, “Dielectric Materials at Microwave Frequencies”, AppliedMicrowave and Wireless.

References


6. Anas Mazady “Non-invasive Glucose Meter”, Electrical and Computer EngineeringDepartment, The University of Connecticut, Storrs, CT 06269-2157

7. Camelia Gabriel, “Compilation of the dielectric properties of body Tissues at RF andmicrowave frequencies”, Physics Department, King's College London, London WC2R 2LS,UK., 1996

8. Anju Pradeep, S. Mridula and P.Mohanan, “Design of an Edge-Coupled Dual- Ring Split-Ring Resonator”, Antennas and Propagation Magazine, IEEE Volume: 53, Page(s): 45 – 54, 2011.

9. Frank Hesmer, et al. “Coupling mechanisms for split ring resonators: Theory and experiment” phys. stat. sol. (b) 244, No. 4, 1170 – 1175 (2007) / DOI10.1002/pssb.200674501, © 2007 WILEY-VCH Weinheim.

10. Christophe Caloz and Tatsuo Itoh, “Electromagnetic Metamaterials: Transmission Line Theory and Microwave Applications”, John Wiley & Sons, INC., Hoboken, New Jersey, 2006.

References


11. FilippoCapolino, “Metamaterials Handbook: Theory and Phenomena of Metamaterials”, CRC Press - Taylor & Francis Group, 2009.

12. Erdem Topsakal, Tutku Karacolak, and Elaine C. Moreland, “Glucose-Dependent Dielectric Properties of Blood P lasma”, 978-1-4244-6051-9 , IEEE , 2011

13. www.wikipedia.com/blood glucose


Thank you !.


Cochin, Kerala59

Electromagnetic sensing of glucose level

• Cole-Cole model is the most well-known for its success to compute permittivity of different cells over a broad frequency range (Gabriel, Lau, & Gabriel, 1996).

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