Non-Invasive Blood Glucose Measuring System

PRESENTED BY: MD. NAJMI ALAM 1MJ07TE027 TELECOMMUNICATION MVJ COLLEGE OF ENGINEERING

Under the guidance of: Mrs. Navya Vipin Asst Prof., Dept. of TE MVJCE Head of the Department Mrs. Savitha H.K Asst Prof., Dept. of TE MVJCE

Diabetes Mellitus
A metabolic disorder in which our body is unable to regulate the level of glucose in the blood

Most prevalent non-communicable disease

More than 150 million diabetic patients in the world

Management of diabetes
Diabetes related long term complications are leading cause of death

The complications can be reduced by 50-75% by tighter glycemic control

Frequent monitoring Adjusting the medical nutritional therapy, exercise and medications to prevent hyper- or hypoglycemia

(Source : The Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long terms complications in insulin-dependent diabetes mellitus, N. Engl. J. Med. 329(14), 977-986 (1993))

Present technique of monitoring blood glucose

Either invasive or minimally invasive Being off-line methodsTime consuming Labour intensive May not reflect real-time status of the glucose can cause cell contamination

Shortcomings of invasive method

Painful High recurring cost
Potential source of spread of diseases like Hepatitis, HIV through contact with bodily fluids Continuous monitoring not possible

Why non-invasive method ?

Will remove all shortcomings of present techniques Improve quality of life Reduce complications and mortality associated with the disease Possibility of developing artificial pancreas

Potential non-invasive optical methods

Infrared and Near-infrared absorption spectroscopy Near-infrared scattering technique Polarimetry technique Raman spectroscopy Photoacoustic spectroscpy

Photoacoustic Method
Modulated laser beam

Excited state

Absorption

Absorption of light Non-radiative transition

Radiative transition

Pressure wave

Sample Ground state

Acoustic transducer

A h

A heat

Factors affecting PA generation

Nanosecond Pulsed Laser Beam

Optical absorption coeff.

Radiative Relaxation

Skin and Tissue

Wavelength Pulse Width, PRF

Local Absorption glucose molecules

Flourescence, Phosphorescence

Local Temperature Increase

Specific heat capacity Vol. expansion coeff.

E T Cp
V

Ei : Incident optical energy a : Absorption coefficient d : Length of the cylinder within the sample occupied by the optical beam Cp : Specific heat capacity for a constant pressure : Density of the medium V : Illuminated volume at room temperature r: Radius of the optical beam i : Volumetric thermal a expansion d coefficient of
the medium B : Bulk modulus T : Rise in temperature

Adiabatic Expansion

TV v : Speed of sound in the medium Ei

a

Pressure Wave Generation

d p

v2

B
p

Ei

B
r

Speed of sound

Cp V
Pressure Detection Transducer

B/

Transducer type & Dimension

Dependence of PA signal on glucose concentration

p

v 2 Cp

E i r

a 2

Offers higher detection sensitivity with simple apparatus More immune to scattering

Phases of development
The total development process has been planned in two phases

Phase I Validation of the technique with glucose solution

Phase II Application on human subject

Block diagram of the proposed noninvasive blood glucose monitoring system

Pulse Generator

Driver Circuit

Laser Diode Piezoelectric Transducer Low Noise Amplifier

Analog to
Digital

DIGITAL SIGNAL PROCESSING BLOCKS

Signal Averager

Fast Fourier Transform

Digital Peak Detector

Calibration Disply Correction Factors

Converter

System Photograph

Choice of components

Acoustic signal detector

Sensitive Rugged Insensitive to changes in ambient conditions

Choice of wavelength

905 nm

905nm 905 nm wavelength gives desired depth of penetration and absorption by Water and other constitutes of blood are less compared to glucose.

Absorption profile of glucose

CG

G M

Comparison between 905 nm and 1064 nm

Parameter
Absorption in tissue

905 nm
Slightly higher than at 1064nm

1064 nm
Lower than at 905nm

Reduced scattering coefficient

Effective penetration depth Absorption in water Absorption in glucose Sensitivity to oxy-hemoglobin and deoxy-hemoglobin Power output of laser diode

Low
Second highest (2.5mm) 0.007 mm-1 Low Less 90 watt

Almost equal
Highest (3.5mm) 0.015mm-1 Very high High 2 watt

Optical source and acoustic detector

Optical source Pulsed Laser diode having = 905 nm Model - PGAS1S12 from EG&G Optoelectronics Pulse width : ~100 ns Pulse repetition frequency : ~100 Hz Pulse energy : Less than 0.1 J/Sq. cm.

Acoustic Detector Piezoelectric material (PZT-5A) from Panametrics, USA

Transducer selection table

LiNbO3 Piezoelectric d33 (10-12 C/N) constant g33 (Vm/N) Mechanical Q factor Density(g/cm3) Sound velocity (m/s) Acoustic impedance(106 kg/m2s) Work temperature(0C) Advantages 6 0.023 100 4.64 7316 33 <1100 Wide band, rugged Expensive PZT-5A 400 0.025 75 7650 4500 35 <360 Inexpensive, High sensitivity Ringing PVDF .39~.44 -0.32 5~10 1.78 2260 4 <60 Wide band, Inexpensive Non-rugged

Disadvantages

Application on human body

Measuring glucose from human body is quite complex due to wide range of potentially interfering components. A number of factors that are to be considered for developing such a system :
a) Optical signal : Depth of penetration at least upto dermis layer of skin Higher absorption by glucose compared to other constitutes of blood, water, protein, fat, melanin etc. Optical energy within the Maximum Permissible Engergy (MPE) as specified in Safe use of lasers for health care facilities, - ANSI Standard Z 136.3-2005 Pulse width and pulse repetition frequency meeting PA generation condition. Test site (e.g. finger, earlobe etc.) Optical signal delivery mechanism

Phase-I : Glucose solution

Carried out PA measurement at 1064 nm using Nd:YAG laser with glucose solution of different concentrations

Result : Peak-to-peak value of the PA signal maintains a nearly linear relationship with the concentration of glucose in the solution.
Conclusion : Can be considered for developing a non-invasive blood glucose monitor

Phase II: on human subject with OGTT

0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0

Point of drinking

10

15

20 25 Time (minute)

30

35

40

Variation of PA signal plotted with digitized signal captured through oscilloscope

Finding : Result closely matches the pattern of variation after consumption of glucose by a subject with the result reported in the literature

Variation of PA amplitude with glucose concentration

80

79
78 77 76 75

74
73 72 71 70 100 105 110 115 120 125 Blood glucose level in mg/dl 130 135 140

Blood glucose values measured with SMBG monitor ACCU CHEK Active

Further work needed to realize the system

Although results achieved so far are quite encouraging, but needs further extensive testing and improvement in the design before it can be considered for clinical use. Modification of the front-end circuitry Design of laser driver circuit Development of Signal Processing Algorithms and implementation in FPGA Nullify the sources of error due to change in

Pressure Temperature (both ambient and body) Melanin content of the skin Oxygen saturation of blood Subject dependent tissue condition at the test site (finger) Any other physiological conditions

BIBLIOGRAPHY
1. Amos AF, McCarty DJ & Zimmett P (1997) The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic Medicine, Supplement 5: S1-S5. 2. Lahmann W, Ludewig HJ, & Welling H (1977) Opto acoustic trace analysis in liquids with the frequency modulated beam of an Argon ion laser. Analytical Chemistry 49: 549-551. 3. Oda S, Sawada T & Kamada H (1978) Determination of ultra trace Cadmium by laser-induced photoacoustic absorption spectroscopy. Analytical Chemistry 50: 865 867.

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