Chapter 1

Introduction
Introduction

Diabetes is known as one of the life threatening diseases in the world that occurs not only
among adults and elderly, but also among infants and children. Blood glucose
measurements are essential for diabetes patients to determine their insulin dose intake and
continuous monitoring is vital to ensure that glucose level is always within the normal range. The
commonly used methods to measure glucose level in blood are invasive which are high in accuracy
but are usually painful and has higher risk of infections. As an alternative, non-invasive
techniques are introduced to develop pain free glucose measuring methods. In this paper, a portable
non-invasive blood glucose monitoring device is developed using near infrared sensors. Besides
being able to detect glucose concentration in blood, the device is also able to display the glucose
level and the required insulin dose, corresponding to the body mass index (BMI) of the user. Several
in vitro and in vivo experiments proved the reliability of the device. Results of the experiments
proved that the device is reliable in glucose detection with 4% - 16% accuracy compared to the
common invasive finger-prick method. The latest technology which is non-invasive has been
introduced as an alternative to reduce pain during the blood extraction and insulin injection. Various
methods have been introduced such as infrared, photoacoustic, ultrasound and fluorescence to
detect glucose in the blood. Most of the results showed a good correlation between non-invasive
and invasive techniques. The major reason for continuous research efforts in the field of non-
invasive blood glucose measurement is that it is the only way to develop a pain free glucose
monitoring system. Instead of extracting blood, other fluids such as the saliva, sweat, urine or tears
can be used as an alternative to measure glucose concentration. Besides that, glucose level can also
be measured through direct measurement of body tissues such as the skin, tongue, aqueous humor
of the eyes and oral mucosa.

Motivation:
Diabetes Mellitus is one of the common life threatening diseases in the world. Malaysia is ranked
10 th in the world with the highest number of population with diabetes (World Health Organization,
(WHO), 2013). The number prevalence increases every year due to the changes of human’s
lifestyles. The main cause of diabetes mellitus is still unrevealed, but it is closely related to body
weight, gender, diet, genetic and physical activities. There are many known factors that can develop
complications in diabetic patients The effects of diabetes can only be seen between six(6) to twelve
(12) months after having continuous high level of glucose in blood, which can further lead to other
major health problems such as kidney failure, heart disease,blindness, stroke and neuropathy. For
example, the possibility of leg amputation in smoking diabetic patients is higher than ordinary
smokers due to blockage of blood vessels which can further lead to a more serious heart
disease. Addition to that, excess of alcohol consumption in diabetic patients can cause nerve
damage and high blood pressure, high blood fats and excess weight gain.

Problem Statement:
Glucose levels had been measured by taking a blood sample from patients which is named
invasive, then analyzed using a spectrophotometer. However, this method is less favorable for
patients with serious conditions or patients with diabetes mellitus who could not do blood sampling
many times. According to that conditions, a development tools of non-invasive measuring glucose
levels in the blood is needed. According to that conditions, a development tools of non-invasive
blood glucose levels measurement is needed. Data analysis should be done by measuring the
percentage error of the measurement results.

Objectives:
1) To build a non invasive blood glucose monitoring system.
2) To analyse glycemic index trends in the subject.
3) Prediction of insulin spikes and spike interval for the subject.
4) Prediction of insulin quantity required to assimilate carbohydrate intake of subject.

1.4 Organization of Report

Chapter 1: Introduction
This chapter includes an introduction of what is Non Invasive Blood Glucose Monitoring.
Chapter 2: Review of Literature
This chapter includes literature papers of various systems which is related to our project
Chapter 3: Requirement analysis
This chapter includes UML use case diagram regarding the working system. It also includes various
hardware and software requirements related to the working system.
Chapter 4: Design

This chapter includes different UML diagrams regarding the working system.
Chapter 5: Report on the Present Investigation:
This chapter gives detailed information about working system. It includes its detailed internal
architecture various related methodologies, working and specifies the input and output of the
system.
Chapter 2
Review of Literature
Non-Invasive Glucose Estimation Based on Near Infrared
Laser Diode Spectroscopy
A noninvasive glucose measurement has been proposed through a process of signal
intensities transmitted through or reflected by the stratum Cornea, dermis layer, epidermis layer,
subcutaneous tissue, interstitial fluid and blood vessel of which both arterial and venous blood are
taken into account. This problem was overcome by means of the following steps: (a) A known
glucose concentration was used to estimate regression equation to plot the best fitting curve for
estimation of glucose concentration in vitro.
(b) Collecting non-invasive signal intensity from non-diabetic individuals and diabetic patients
using the proposed kit.
(c) Blood sample was taken from the same subjects invasively and the glucose oxidase method
(GOD and POD method) of estimation of glucose concentration was done.
(d) Computing the values based on the correlation between measured blood glucose values and non-
invasive signal intensities and a graph is plotted.

Results Obtained in this system are plotted below:

Design of Digital Blood Glucose Meter Based
on Arduino UNO
In this system a special biosensor is created which is used to detect glucose levels. A biosensor is
a sensor that makes use of biological or living material for its sensing function. There are three main
parts of a biosensor: (i)biological detection elements, which recognize the substance of interest, (ii)
a transducer, which converts the biorecognition event into a measurable signal and (iii) a signal
processing system, which converts the signal into a workable form. The basic operation of glucose
biosensor is based on the fact that the enzyme glucose oxidize(GOD) catalyses the oxidation of
glucose to gluconic acid. The enzyme acts as a biorecognition element, which recognizes glucose
molecules. These enzyme molecules are located on an electrode surface, which acts as a transducer.
As soon as the enzyme recognizes the glucose molecules, it acts as a catalyst to produce gluconic
acid and hydrogen peroxide from glucose and oxygen from the air. The electrode recognizes the
number of electron transfer due to hydrogen peroxide/oxygen coupling. This electron flow is
proportional to the number of glucose molecules present in blood. The glucose sensor is an
electrochemical diagnostic strip which uses glucose oxidizes enzymes in conjunction with three
electrically conductive electrodes. Two of these electrodes are working electrodes meaning they are
the measured electrodes, and the third is a reference electrode as shown in Figure. The signals
from glucose sensor are transmitted to next stage of signal condition unit. The output of the
Biosensor is connected to INA219 Current Sensing.

Chapte
r5
Report
on
Presen
t
Investi
gation
 Proposed System:
The proposed system is focused on development of non-invasive blood glucose
measurement sensor system using Near-infrared (NIR) technique. Initially in-vitro glucose
measurement prototype is developed using continuous wave (CW) from NIR LED (940 nm) to
check the sensitivity of the system for different glucose concentrations. Later a Sensor patch is to be
designed using LED and a photodiode to observe diffused reflectance spectra of blood from the
human forearm.

As the radiation interacts with biological tissue, it is attenuated by absorption as well as scattering.
The attenuation of light can be described by light transport theory:

here g is anisotropy factor and μ ୱ is scattering coefficient. Variation in glucose concentration

affects the intensity of light scattered from tissue. Light scattering involves the change in refractive
index mismatch of extra cellular fluids (ECF) and membrane of cells. The value of refractive index
of ECF is approximately 1.348-1.352. Whereas refractive index of blood cells is approximately
1.350-1.460.
At present none of the available methods can cure diabetes completely. Occurrence of
complications can be prevented by keeping blood glucose levels in the normal range.
Regular glucose monitoring, diet plan, insulin shots and oral medications are the foundation of
diabetes treatment. Regular blood glucose monitoring is the key step in efficient management of
diabetes to control blood glucose. Most of commercially available glucose measurement
devices are invasive. Diabetic patients need to monitor their blood glucose two to three times a day.
The invasive methods are painful, have high recurring cost and danger of spreading infectious
diseases. Non-invasive methods are more desirable and excellent alternatives to these devices.
Enhancing glucose measurement techniques to allow easy and continuous monitoring has received a
lot of attention from both academic and industrial researchers over the past three decades. Non-
invasive glucose monitoring could make millions of people more relaxed and comfortable about
blood glucose testing. Thus it is necessary to develop a non-invasive blood glucose method which
can provide painless, convenient and cost effective glucose monitoring to diabetic patients.

The modules of the system are as follows:

1) Blood Glucose Level Monitor Module: This module consists of the hardware module that will
have a photoplethyschemographic assembly which will measure the blood flow and send the signal
to the microcontroller. The microcontroller will then load a look up table which will have the
glucose indication threshold data for different blood pressure volumes. Through the lookup it will
display blood glucose level on screen and the data will be shared with the paired Android device
(user’s smartphone).

2) Glucose Monitor Android Application: The glucose meter will have a companion Android
application which will synchronize all the data received from the user end via the gluco-meter and
store it as a historic data for user’s personalized insulin profile. After a few days of regular use and
monitoring user’s insulin profile, it will recommend user about the nature of his insulin spikes and
the approximate glycemic index effect of the carbs intake. It will also recommend user things to
keep his glucose levels in check.
 Selecti
on of
wavel
ength
and
transd
ucer
materi
al for
glucos
e
sensor
:

Near-
infrare
d
Spectr
oscop
y
(NIRS
) uses
the
light
in
750- 2500 nm region which interrogates the tissue with low- energy radiation. No specific reagents
are required for measurement, so repetitive analysis can be performed at low cost. NIR radiation in
700-1100nm is considered as therapeutic window, as it allows the glucose measurement up to the
depth of few mm under the skin. Glucose has absorption peaks at 939nm, 970nm, 1197nm in higher
overtone region, 1408nm, 1536nm, 1688nm, 1925nm in first overtone region and 2100nm, 2261nm,
2326nm in combination region. For present design NIR LED at 940nm wavelength (FGA10) is
used. Although glucose has less absorption at 940nm as compared with first overtone and
combination region, but due to minimum attenuation of optical signal by other constituents such as
water etc, desired depth of penetration can be achieved at this wavelength. LED based sensor
system is preferred for present work as it overcomes all the limitations of LASER. As LASER have
higher construction cost, larger space for making the instrument and more instrument space for
cooling. In comparison LED is smaller in size, lower cost, requires less power, no extra circuit is
required for cooling, and causes less damage to tissue. Thus LED based system would be low cost
and portable alternative to LASER based systems. Photodiodes is used to detect the attenuation of
radiation due to changes in the glucose concentration.