U.A. NADKARNI MSc THESIS - Copy

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U. A. Nadkarni
Health Tracker: Biosensors
SCHOOL OF HEALTH
Medical Diagnostics
MSc THESIS
Academic Year 2013 - 2014
Supervisor: J. D. Newman
September 2014
This thesis is submitted in partial fulfilment (40% weighting) of the
Requirements for the degree of Master of Science
© Cranfield University 2014. All rights reserved. No part of this publication
May be reproduced without the written permission of the copyright owner.

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Abstract
In this project Health Tracker : Biosensors attempt is made to rationalise the meaning of
wellbeing and various health tracker parameters by which this health wellbeing can be
assessed is discussed. The importance of changing trend of diseases and morbidity and
mortality worldwide both in developed & developing world is projected and further attempt
is made to reason out why chronic condition such as Diabetes Mellitus needs to be tackled
head on. The importance of Biosensor in health tracking the blood glucose check regularly
and proposed methods and laboratory method used is rationalised.
Finally the actual laboratory experiments carried out, the results produced and their
interpretation is discussed and conclusions drawn to complete the project.

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Acknowledgements
I am grateful for all the help I received from my supervisors, Dr Jeffrey Newman and
Professor Selwayan Saini, Inside Biometrics Ltd for their support and guidance throughout
my dissertation.
I would also like to give a special thanks to my family, especially my mother and my father
for their continued support and encouragement throughout my studies.

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Table of Contents
Page
Abstract 2
Abbreviations 11-12
Chapter 1 Introduction and Literature Review 13
1.1 General Introduction 13-14
1.2 Assessment of Wellbeing (Measurement) 14-15
1.3 Methods for monitoring wellbeing 15
2.0 Health trackers (Prioritized List) 15
2.1 Blood Glucose 15-16
2.2 HbA1c (Glycated Haemoglobin) 16
2.3 Blood RBC's & WBC's 17
2.4 Cholesterol/HDL/LDL 17-18
2.5 Blood Pressure 18-19
2.6 Electrocardiogram (ECG) 19-20
2.7 Heart Rate 20
2.8 Respiratory Rate 20-21
2.9 Blood pH 21
2.10 Body Temperature 21-22
2.11 Exercise Lactate 22
2.12 Body Mass Index (BMI) 22-23
2.13 Blood Alcohol 23
2.14 K+
(Potassium) 23-24
2.15 Drugs of Abuse 24
3.0 Opportunities for measurements of Health Tracker Parameters/Indices/Markers 25
3.1 Diabetes Mellitus 25-27

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3.2 Infectious Diseases 27-28
3.3 Malnutrition 28
3.4 Mental illness 28-29
3.5 CHD (Coronary Heart Disease) 29
3.6 Cancer 30
3.7 COAD (Chronic Obstructive Airway Disease) 30-31
4.1 Disease Prevalence and Incidence 31-40
4.2 Burden of Disease and Cost Effectiveness Estimates 40
4.3 Effectiveness of monitoring 41-42
5.1 Aims 42
5.2 Objectives 42
6.1 Monitoring Systems 42-43
6.1.1 Physiological sensors 43-45
6.2 Chemical sensors 45-46
6.3 Remote Sensors 46-47
6.4.1 Biosensors 47
6.4.2 Market & Applications 48
6.4.3 The Basic Components of Biosensors 48-49
6.4.4 Requirements of Biosensors 50
6.4.5 Transducer/ Bio transducer 51
6.4.6 Functioning of Biosensor 51
6.4.7 Classification of Biosensors 51-52
6.5 Glucose Biosensors 52-53
6.5.1 A brief historical perspective of glucose sensing 53
6.5.2 Generations of Biosensors 53
6.5.3 First Generation Glucose Biosensors 54
6.5.4 2nd Generation Glucose Biosensors 54
6.6.1 Problems to surmount in Glucose Biosensors 54
6.6.2 Enzyme Interferences 55
6.6.3 Electrode Interference 55

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6.6.4 Fouling 56
6.7.1 Measurement by finger pricking (Point of Care) 56
6.7.2 Continuous Measurement of Glucose 56-57
6.7.3 Non-invasive Glucose Measurements by sensors 57
6.8.1 Enzymes and their mechanisms of action 57-58
6.8.2 Methods of Immobilisation of Enzymes (with Advantages and disadvantage58
6.8.3 Physical Adsorption 58
6.8.4 Enzyme Entrapment 58
6.8.5 Micro Encapsulation 59
6.8.6 Cross Linking 59
6.8.7 Covalent Bonding 59
6.9 Various uses of Enzyme (Glucose Oxidase GOx) 59-60
Chapter 2 Materials & Methods 61
1.1 Materials & Methods (for Electrochemical Biosensors) 61
1.2 Biological Recognition Element 61
2.1 Material for Electrodes and Supporting Substrates 61-62
2.2 Membrane Materials 62
2.3 Materials for immobilisation of Biological Recognition Elements 62-63
3.1 Methods for Fabrication 63
3.2 Electrode Fabrication Methods in current use 63-64
3.2.1 Screen Printing 64
3.2.2 Deposition Method 64
3.2.3 Polymerisation 64
3.2.4 Plasma Induced Polymerisation 64
3.2.5 Photolithography 65
3.2.6 Nanotechnology 65
Chapter 3 Rationalisation 66

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1.1 My proposed Method for the Glucose measuring Device and Schematic plan (What
can we do better?) 66
1.2 Fabrication of Electrode (working electrode) 66
1.3 Construction of outer membrane 67
2.1 Rationalisation 67-70
2.2 History of Glucometer 71
Chapter 4 Design of Device 72
1.1 Apparatus – Electrodes Construction 72
1.2 Reference Electrode 72
1.3 Counter Electrode 72
1.4 Enzyme Electrode Construction 73
1.5 Construction of Membrane layer 73
1.6 Preparation of Buffers solution 74
1.7 Preparation of Glucose Solutions for Testing 74
1.8 Experimental Method and Application of Membranes 74-75
1.9 Equipment used 75-76
Chapter 5 Results from Device 77
1.1: Sensor 1 Buffer 77
1.2: Sensor 1 1mM 77
1.3: Sensor 1 5mM 77-78
1.4: Sensor 1 10mM 78
1.5: Sensor 1 100mM 78-79
1.6: Concentration Vs Current : Sensor 1 79
1.7: Sensor 2 Buffer 80
1.8: Sensor 2 1mM 80
1.9: Sensor 2 5mM 80-81
1.10: Sensor 2 10mM 81

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1.11: Sensor 2 100mM 81-82
1.12: Concentration Vs Current: Sensor 2 82
Chapter 6 Discussion / Conclusions 83
References 84-87
Appendices 88-91

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List of Tables
Table 1 : Prevalence (millions) of selected conditions by WHO region; 2004 32
Table 2 : Incidence in (millions) of selected conditions by WHO region; 2004 34
Table 3: Incidence in (millions) of selected conditions by WHO region; 2004 39

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List of Figures
Figure 1: The major waves of a single normal ECG pattern 20
Figure 2 : Worldwide distribution of diabetes prevalence in 2005 and estimated numbers for
2030 (adapted from WHO, 2004) 25
Figure 3: The 10 leading causes of death in the world; WHO (2014) 35
Figure 4: The 10 leading causes of death in the world by percentage; WHO (2014) 36
Figure 5: The 10 leading causes of death in the United States in 1900 and 1997; 2014 38
Figure 6: Mote1 Form factor; Sensor: ECG, Temperature, GSR, Accelerometer 43
Figure 7: Mote 2: Form factor; Sensor: Respiratory Inductive Plethysmograph (RIP) 44
Figure 8: Bridge Mote Form Factor 44
Figure 9: End – to – End System 44-45
Figure 10: Signal Captured from the Autosense System on a laptop appears below: Red is
Respiration and Green is the ECG. 45
Figure 11: Composition of Chemical Sensor 46
Figure 12: A LIDAR (Light Detection and Ranging ) Image created with data collected by
NOAA’s National Geodetic Service 47
Figure 13 Schematic diagram showing the main components of a biosensor 49
Figure 14: Working principles of a Biosensor 49
Figure 15: Glucose Detector 49
Figure 16: Principles of different enzyme immobilisation methods (adapted by Turner.et.al;
1987) 58
Figure 17: Anton H. Clemens (right) was the inventor of the first blood glucose meter while
he was the director of the Ames Instrument R&D Department of the Ames Division of Miles
Laboratories Inc. in Elkhart, Indiana. Here he is shown talking to George W. Orr, Jr., Group
Vice President, Professional Products Group (left) and Walter Ames Compton, M.D.,
President and Chief Executive Officer of Miles Laboratories Inc. (centre). This photograph
appeared in the 1969 Annual Report of Miles Laboratories Inc.; Mendoza, D. (11/1999),
Blood Glucose Meters, available at: www.mendosa.com/bgmeters.htm (accessed 07/2014).
70-71

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Abbreviations
CDC Centres for Disease Control & Prevention
WHO World Health Organization
PSI Public Services International
WHO World Health Organization
HIA Health impact Assessment
DALY Disability Adjusted Life Year
EIA Environmental Impact Assessment
HIA Health Impact Assessment
AIDS Acquired Immunodeficiency Syndrome
HIV human immunodeficiency virus
STD Sexually Transmitted Diseases
NHIS National Health Interview Survey
HRQOL Health-Related Quality of Life
C6H12O6 Glucose
C2H5OH. Alcohol
ECG Electrocardiogram
BMI Body Mass Index
HbA1c Glycated Haemoglobin
LDL Low density Lipoprotein
HDL High density Lipoprotein
VLDL Very low Density Lipoprotein
NHLI National Heart & Lung Institute
GABA Gamma amino butyric acid
PET scan Positron Emission Tomography
NIDA National Institute on Drug Abuse
BAC Blood Alcohol Concentration

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CHD Coronary Heart Disease
COAD Chronic Obstructive Airway Disease
GBD Global Burden of Disease
MPKB The Marshall Protocol Knowledge Base
SCR Skin conductance Response
GOx Glucose Oxidase
H2O2 Hydrogen peroxide
KCl Potassium chloride
FAD Flavine adenine dinucleotide
NAD Nicotine adenine dinucleotide
GDH Glucose dehydrogenase
PQQ Pyrroloquinoline quinone
ISE Ion-selective electrode
ISF Interstitial fluid
Pt Platinum
SD Store Data
TBATS TetrabutylammoniumToluene Sulphonate
POC Point of Care
FET Field Effective Transistors
AFM Atomic Force Microscopy
PEG Polyethylene Glycol
ARM Ames Reflectance Meter
HEC Hydroxylethyl cellulose
BGM Blood Glucose Monitoring

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CHAPTER I: INTRODUCTION AND LITERATURE REVIEW
1.1 General Introduction:
According to World Health Organization (WHO) Health is defined as "A State of complete
physical, mental and social well-being and not merely the absence of disease or infirmity" the
correct bibliographic citation for this definition is Preamble to the constitution of the World
Health Organization as adapted by the International Health Conference, New York 19-22
June, 1946; signed on 22nd
July 1946 by the representatives of 61states and entered into force
on 7th
April 1948( As shown in official records of the World Health Organization no2 p. 100)
reproduced : http://www.who.int/about/definition/en/print.html
There has been no change or modifications to date to this definition, though there are moves
recently in that direction. WHO has stated that "The enjoyment of the highest attainable
standard of Health is one of the fundamental rights of every human being without distinction
of race, religion, political belief, economic or social conditions" reproduced: PSI ,
http://www.world-psi.org . In 21st
Century apart from absence of disease or illness, health
has to take into consideration other factors such as to person's emotional, social and mental
factors ultimately connected to his or her happiness and life satisfaction, thus broadening the
view. Even according to Centres for Disease Control & Prevention (CDC), healthy mind and
healthy body together help in Health promotion and naturally increase a sense of individuals
other economically related benefits. This also increases his/her longevity of life, and person's
productive contribution and connectivity to society.
All this contributes to National wellbeing. Attempts have been made by researcher in
Australia & America to measure National Health but it is difficult though it is important to
realise that higher levels of well-being are more productive with positive contribution to
societies as seen in Developed world.
Public Services International (PSI), a global trade union represents 20 million workers
delivering vital services in 150 countries. In an article published on PSI "Health is a public
good and ill health is a fundamental humanitarian problem with political, economic and
social causes and consequences" reproduced: PSI, http://www.world-psi.org. In general
higher levels of wellbeing is seen more in economically developed countries. They have
more effective and accountable governments with lesser degree of corruption and manage
their citizen's needs of food & health.

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The world Health Organisation (WHO) recognised the need for developmental policies. To
promote rather than compromise health to reduce the negative health impact it advocated
inclusion of Health component in its environmental impact assessment. There is also
included Health impact Assessment (HIA) (CooperWeil.et.al 1990). Unfortunately Health
Professional; who should really be an integral part of any development and may thus find it
uncomfortable to participate in EIA process e.g. building highway through very thinly
populated area may not require much health planning input but if a large dam is to be
constructed passing through densely populated subtropical countries with high levels of
AIDS and vector borne diseases, like malaria, it would need expertise in environmental
health & health promotion. Hence health impact assessments include integrated steps of
review, research, socio demographic assessment to assess population at risk, health
determinant assessments (water & sanitation, food, housing, fuel security, pollution, public
infrastructure, waste management etc. which affect health.
The other factors included are Health status assessment such as quantitative assessment in
terms of morbidity & mortality due to diseases, conditions & injuries; and World Bank has
brought it out (WHO 1996) in terms of Disability Adjusted Life Year (DALY) discussed
under section 4.3. The other assessments need to be done are regarding Health Services
deliveries in terms maternal & child health promotion, family planning, STD clinics,
Hospitals, community Health workers etc. This really is a gigantic task but HIA planning
needs to be really good if populations are to secure their wellbeing in terms of housing, job
satisfaction, social connectivity, neighbourhood security etc. mentioned above.
Unfortunately developing countries rather than developed ones, who need this planning, with
their limited resources and local EIA and HIA planning facilities have more problems in
coping with this task.
1.2 Assessment of wellbeing (measurement)
Wellbeing is difficult to quantify and thus difficult to measure as it is more subjective
assessment by an individual himself of his own condition and expressed in his own words.
However NHIS (National Health Interview Survey in 2001- NHIS 2001) was carried out
using also some objective parameters such as individual satisfaction regards his basic needs
of job & income, housing, neighbourhood, social relationship etc. The combination of these
subjective and objective indices which are called Psychometric & utility based techniques is a
more useful method of measurement. To assess perhaps the National wellbeing the index
was placed between 0(death) to 1(optimum health) at the two extreme points. On this scale
males or females between ages of 20-39 years measured significantly better wellbeing (scores
≥0.82) compared to males and females 40 years or older (scores ≥0.79) . Reproduced: CDC,
(Health-Related Quality of Life (HRQOL) Wellbeing Concepts
http://www.cdc.gov/hrqol/wellbeing.htm).
Data from 2005 Behavioural Risk Factor Surveillance Electrochemical biosensors:
Recommended definitions and classification Thévenot, D.R., Toth, K., Durst, R.A., Wilson,
G.S. 2001 Biosensors and Bioelectronics 16 (1-2), pp. 121-131system(BRFSS) in USA

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demonstrates 5.6% of US adults were dissatisfied/very dissatisfied with their lives but Porter
Novelli Health style data (2008) reveals 30% adults most days feel sense of accomplishment
from what they do. Reproduced: CDC, (Health-Related Quality of Life (HRQOL) Wellbeing
Concepts http://www.cdc.gov/hrqol/wellbeing.htm).
Apart from National level, at individual level genetic factors, personality and demographic
come into play. In general there is found to be U-shaped distribution of wellbeing age wise.
Younger and older adults to have more wellbeing compared to middle-aged individuals who
are subject to more stress and have responsibilities still to fulfil. There is now thus a move
towards measuring the health of individuals in more holistic way (physical + mental health)
Reproduced: CDC, Health-Related Quality of Life (HRQOL) Wellbeing Concepts
http://www.cdc.gov/hrqol/wellbeing.htm.
Incidentally mental health is defined as "a state of wellbeing in which every individual
realises his or her own potential, can cope with the normal stresses of life, can work
productively and fruitfully and is able to make a contribution to her or his community".
Reproduced: CDC, Health-Related Quality of Life (HRQOL) Wellbeing Concepts
http://www.cdc.gov/hrqol/wellbeing.htm. There is therefore now a move at WHO to broaden
the definition of Health. There has also been an attempt to measure the health at National and
International levels. Such attempts have been made in Australia and in America but it is
difficult due to obvious gigantic nature of the task though the attempts are further continuing
in the matter.
1.3 Methods for Monitoring Well-Being
With advances in physics and chemistry and various subspecialties such as electrochemistry,
optical physics e.g. Raman Spectroscopy, especially in the field of nanotechnology the things
have taken a quantum jump in the quantitative assessment of health monitoring systems in
medicine & other fields. In medicine in particular ability has now been achieved to measure
various parameters/indices pertaining to individual health and I shall discuss some of them
briefly in the discussion that follows.
I shall now underneath mention some of the body's indices/parameters/markers that are
routinely measured by Health Tracker and discuss them briefly.
2. Health Trackers (Prioritized List):
2.1 Blood Glucose:
All the cells in our bodies need for physiological processes or metabolism energy which is
supplied by Glucose transported in blood. The glucose is produced from all the food we eat.
The human body normally regulates blood sugar levels strictly within a narrow range of 4-
7mmol/80-120mg so as not to be too high or too low in order to maintain stability and

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equilibrium of internal environment called Homeostasis. Post prandially (after 2 hours of
meal), the normal variation is ≤140mg/dl (7.8mmol/l). With passing age e.g. after 60 this
level is a little higher 8.9mmol or ≤160mg/dl due to increasing glucose intolerance.
Sugar or glucose is a simple form of carbohydrate body make into, prior to use by cells
particularly brain cells which need steady supply of glucose (C6H12O6). The Glucose
however can enter cells only in the presence of Hormone (Insulin) secreted by the βcells of
pancreas, an abdominal organ. The release of this hormone in the body is controlled by what
is called feedback mechanism with supervisional control by central nervous system. In the
healthy body excess glucose is converted to Glycogen (a form of polysaccharide) by liver and
muscles. Derangement of this normal control mechanism by either autoimmune destruction
of βcells of Pancreas or a condition of Insulin resistance results in a pathology of chronic
hyperglycaemia (called Diabetes Mellitus). If the blood sugar is excessive while passing
through kidney it may not be absorbed being thrown out in urine producing what is called
Glycosuria. On the other hand tumour of βcells called Insulinoma or more commonly excess
or erroneous intake of antidiabetic medication may result in low blood sugar called
hypoglycaemia which is much more serious. A stage of Biochemical or absolute
Hypoglycaemia is reached when blood sugar falls to below 2.2 milli moles/litre. This can
cause serious damage to all but more important to central nervous system and life
threatening.
Various forms of blood glucose estimations are done including Fasting blood glucose,
Random sample, postprandial (2 hours after meal), and Oral glucose tolerance especially in
pre- diabetics depending on indication. For overall review of maintenance of Diabetic
control Glycated Haemoglobin (called HbA1c) measure which is popular test at present
described below. Ref: Diabetes Health Centre: Blood Glucose;
http://www.webmd.com/diabetes/blood-glucose
2.2 HbA1c (Glycated Haemoglobin):
As stated above this test is routinely used in Diabetics to evaluate Glycaemic control in
previous 6-12 weeks and thus to adjust medications and other measures in conjunction with
home blood glucose monitoring. The normal range of glycated Hb is between 4% to 5.6%.
Between 5.6% - 6.4% there is increased risk of Diabetes. In known diabetics aim is usually
to maintain level to at least less than 7%. The normal lifespan of RBC's is approximately 120
days and they especially in their latter span glycate excess glucose. Hence this gives idea of
Diabetic control in previous 6 - 12 weeks. Higher levels of HbA1c leaves the risk of
Diabetes related complications of cardiovascular conditions of Heart disease and strokes.
In Diabetics regular 3 monthly checks are required but in well controlled ones, 6monthly
check-ups of HbA1c suffice.
Anaemia, liver and kidney disease, high cholesterol levels and Vitamin C adversely affect
results of this test. Ref: Diabetes Health Centre: The Haemoglobin A1c (HbA1c) Test for
Diabetes http://www.webmd.com/diabetes/guide/glycated-hemoglobin-test-hba1c

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2.3 Blood RBC's & WBC's
RBC's, WBC's & Platelets are cellular components of blood the fluid component being
plasma; RBC's & WBC's & Platelets are formed in the marrow of the bones namely the red
marrow usually from the flat bones such as ribs, skull bones, breast bone(Sternum), hipbones,
and thigh bones in early childhood when red marrow still exists. The normal RBC count is
approximately 5 million/cc in males & 4.5 million/cc in females. The corresponding figure
of normality for WBC being (4.0 -11.0/cc). Low Oxygen Tension or Hypoxia e.g. at high
mountains or anaemia (Low RBC count) is a stimulus for production of more RBC's, the
other factor being Erythropoietin a hormone produced by the kidneys. The main function of
RBC's is to carry O2 from lungs to tissues by loosely binding it to specialised protein in it
called Haemoglobin and after dissociation of this O2 in tissues collect CO2 from them by use
of enzyme called carbonic anhydrase and to deliver it to lungs through capillaries for loss by
exhalation. The peculiar biconcave shape of RBC's and it's a nucleate nature in matured
RBC's in blood makes it more efficient in this process.
The WBC's on the other hand perform the function of Defence and immunity and are
nucleate in nature. Normally of different types including granulocytes e.g. neutrophils,
eosinophils, basophils and others such as lymphocytes and monocytes involved in immunity
& phagocytosis of larger particles. Neutrophils are increased in acute infections, eosinophil's
in allergic & worm infestations. The normal life span of RBC's is 120 days; that of WBC's
varies from 24 hours to many days depending upon the nature of the cell. The normal RBC's
and WBC's counts are a sign of good health. Ref: how stuff works "Red Blood Cells"
http://health.howstuffworks.com/human-body/systems/circulatory/blood1.htm
Having enumerated some of the health tracker (parameters/indices/markers), I believe it
would be entirely be appropriate to mention in brief common conditions met with in routine
practice (individually, nationally and internationally) where measuring these
parameters/indices/markers prove vital and help immensely in finding relief and control for
conditions. I shall mention these opportunities below. It is also important to study the
prevalence and incidence of disease, changes in the pattern of conditions which used to be top
killers in the past 2 centuries and current trend in conjunction with burden of disease and cost
effectiveness to realise the impact on wellbeing and the importance of measuring
effectiveness of monitoring. This is particularly so because in this jet age millions of people
travel to and fro and communicate globally. The advent of internet and TV also makes
people more aware and anxious about the matters and the concept of global village makes it
fully appropriate.
2.4 Cholesterol/HDL/LDL:
This is a wax like fatty substance required in the body in the production and maintenance of
cell walls or membranes, Vitamin D and bile acids required in the digestion of fat. It also is
required for the production of hormones such as steroid hormones. It is produced in the body

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by liver and other cells. The external important food sources are eggs, meat and dairy
products including milk and its derivatives. Though important, body needs cholesterol in
only small quantities. Excess of it in blood however causes deposition on the inner lining of
vessel walls in the form of hard waxy layer called Plaques. Over the years it leads to
narrowing and hardening of blood vessel with impediment to blood flow especially in
Diabetics in whom the cholesterol levels tend to remain high. The serious consequences such
as chest pain (Angina), Heart attack (myocardial infarction) or cerebral strokes can follow
depending on the blood vessels involved and level of involvement. These situations cost
considerably not only to affected individual but also to the family, society and government as
such in terms of monitory, social, productivity, morbidity and mortality. Hence the
importance of maintaining normal levels of Blood cholesterol. Cholesterol travels in blood
attached to protein; this combination is called Lipoprotein and depending on the amount of
proteins in relation to fat there are normally 3 types of Lipoproteins:
i. Low density Lipoprotein (LDL) : - called bad cholesterol resulting in plaques
ii. High density Lipoprotein (HDL): - good cholesterol as lower risk of Heart disease
iii. Very low Density Lipoprotein (VLDL): - mostly fats & non proteins
Excess of fats, calories; alcohol etc. get converted to (iv) triglycerides or simply stored as fat.
The normal LDL values remain between 100 - 129mg/dl. Above 160/dl are considered high.
Similarly for Triglycerides<150mg/dl are considered normal, above 200 mg/dl high
Factors such as diet (high fat diet), Diabetes, age, gender and overweight and, smoking affect
cholesterol levels adversely. On the other hand, good exercise, low fat diet and medicines
such as statins lower the cholesterol levels. Ref: Cholesterol & Triglycerides Health Centre;
The BasicsofCholesterol http://www.webmd.com/cholesterol-management/guide/cholesterol-
basics; Cholesterol & Triglycerides Health Centre: http://www.webmd.com/cholesterol-
management/guide/understanding-numbers
2.5 Blood Pressure:
Blood pressure is the force of blood pushing against the artery walls each time the heart
pumps the blood into the vessels to supply organs and tissues. Its importance lies in the fact
that it is the pressure against which heart has to pump and exert. Hence High blood pressure
strains the heart. Usually this is associated with narrowed blood vessels by cholesterol
plaques as mentioned above under cholesterol and can lead to heart attacks and strokes.
The blood pressure can be measured by doctors or nurses traditionally by using mercury
manometers cuff and stethoscope. This gives upper and lower readings called systolic and
diastolic blood pressures. Systolic is normally a reading produced by contraction of the heart
(systole) and diastolic by its relaxation (diastole - filling phase). Normal values of blood
pressure as advised by National Heart & Lung Institute (NHLI) are 120/80mmHg, 120-129

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systolic - Prehypertension, 80 - 89 diastolic prehypertension (140systolic & above and 90 &
above diastolic Hypertension). It is the diastolic blood pressure which gives idea roughly
about the duration of Hypertension and also the condition of vessels and associated macro
vascular risks.
Hypertension usually is of two types due to unknown cause (essential or idiopathic &
secondary follow causes e.g. Kidney disease, disease of the adrenal glands etc.
The blood pressure can be affected by various factors such as Age, gender, emotional status,
time of the day, exercise, rest, smoking and drinking habits, high salt diet, Diabetes, High
Cholesterol in Afro Americans, etc... Hence its regular check by a common man at home
using aneroid and digital barometer to avoid risk of mercurial manometers, is important in
maintaining it, as well as taking repeat readings on different occasions before stamping
somebody as hypertensive is important.
Ref: High blood pressure (hypertension)
http://www.nhs.uk/conditions/blood-pressure-(high)/Pages/Introduction.aspx
2.6 Electrocardiogram (ECG):
This is a test, as the name suggests, checks the problems with electrical activity of the heart.
The ECG translates this electrical activity into a line tracing on a special paper. The spikes
and dips in the line tracings are called waves and are denoted by the alphabets PQRST. The
heart is a muscular pump made up of 4 chambers. Upper two are called atria and lower two
ventricles. A natural electrical system in the heart makes it contract and pump the blood into
lungs and rest of the body. An electrocardiogram is done using usually a portable machine
with a set of wires called leads that are connected to various parts of the limbs and chest to
get tracing from different angles of heart. Usually a 12 lead tracing is obtained. In hospital
sometimes a continuous monitoring is done by ECG what is called Telemetry. Tracing of
ECG gives idea about its rate (normal 60 - 100 beats per minute) or too fast or too slow as
well as whether it is regular or irregular.
As stated above ECG can be done to check heart's electrical activity to know unexplained
cause of chest pain (e.g. myocardial infarction, angina or inflammation of sacs of heart
(pericarditis). It is also done to note cause and type of irregular heartbeats (Palpitations),
shortness of breath or dizziness, to know whether heart walls are thickened (Hypertrophied),
the effectiveness of heart medicines and their side effects (toxicity) can also be assessed by
ECG, as well as the working of implanted mechanical devices (e.g. Pacemakers) and health
of the heart in disease conditions such as cigarette smoking, diabetes or high blood pressure.
Ref: Heart Disease Health Centre: Electrocardiogram http://www.webmd.com/heart-
disease/electrocardiogram

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Figure 1: The major waves of a single normal ECG pattern How to read an
Electrocardiogram (ECG). Part One: Basic principles of the ECG. The normal ECG
http://www.southsudanmedicaljournal.com/archive/may-2010/how-to-read-an-
electrocardiogram-ecg.-part-one-basic-principles-of-the-ecg.-the-normal-ecg.html
2.7 Heart Rate:
Heart rate is the rate at which the heart beats per minute. In the normal individual the heart
rate is usually given by Pulse rate felt easily by palpating at wrists (Radials), neck (Carotid),
or groins (Femoral) or over the temples (Temporal). If the heart is irregular then it may be
necessary to listen directly to chest over area of heart with stethoscope. Normal heart beats
between 60 - 100per minute at rest. The rate is easily affected by exercise, fever, emotions,
"fright or flight" and drugs such as Digoxin or β blockers as well as drug or substances of
abuse.
In the child at birth the rate is highest which slowly with growth adolescence and adulthood
settles to within normal limits. The athletes achieve slow pulse rate by their regular rigorous
training. The volume of the pulse also provides some indication about functioning of the
heart. The heart rate can also be monitored by machines.
Ref: Heart Disease Health Centre: Pulse Measurement; http//www.webmd.com/heart-
disease/pulse-measurement
2.8 Respiratory Rate:
Respiratory rate is simply the rate of breathing which is the number of breaths per minute.
The rate is assessed at rest and measured by number of times the chest rises per minute when
the person is lying down. Respiratory rate increases with fever, illness and other medical
conditions and drugs and substances of abuse. When checking respiration it is important also
to note whether the person has any difficulty in breathing. The normal respiratory rate in
adults is between 12-18 breaths per minute. Once again the normal respiratory rate in

21
humans is the highest at birth(in infancy 40 - 60/min) and growing through childhood and
adolescence settles down to adulthood rate (12 - 18/minute).
Ref: Vital Signs (Body Temperature, Pulse Rate, Respiration Rate, Blood Pressure)
http://www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=85,P00866
2.9 Blood pH:
By definition PH is the inverse logarithm of hydrogen ion concentration of any given
solution. The pH of 7 is considered neutral. The normal body pH is 7.4 which is slightly
alkaline. The Hydrogen ions are extremely reactive and can affect some of the important
molecules involved in body's physiology. The normal physiology of body only functions
within a very narrow range of deviation (7.35 - 7.45). The pH change to below 6.9(severe
acidosis) and above 7.9(severe alkalosis) can have serious life threatening consequences and
are not compatible with life if the change lasts more than short while.
Thus to maintain the body's internal environment harmony, the blood has a system of buffer
pairs; namely a mixtures of two chemicals, weak acids which resist the pH change from
normality by either accepting or donating Hydrogen ion. The most important organs
concerned with this pH maintenance are lungs and kidneys. The most important buffer pair
in humans is Bicarbonate/Carbon Dioxide pair acting at the level of excretion by lungs. The
other buffer pairs are Proteins and Phosphates. The kidneys regulate Bicarbonates and some
non-volatile acids produced in metabolism through renal excretion with ultimate pH control.
Ref: Lecture Notes-39: Regulation of Blood pH Kidneys and Lungs
http://acccn.net/bio/book/bio50/lecnotes/lecnot39.html
2.10 Body Temperature:
Body Temperature is simply the temperature of the body and is an indicator of Body's ability
to generate heat under certain conditions and to get rid of it when necessary, thereby
maintaining a constant temperature for proper functioning and constancy of internal body
environment or Homeostasis. Normal temperature of body varies between (36.50
C - 37.20
C
or 97.80
F - 99.00
F) irrespective of outside temperature. Normally body maintains this
excellently through its dermal or skin surface. In hot and humid conditions there is
proportional dilatation of skin vessels. The person sweats thus, evaporation of which as well
as by radiation and convection heat is lost to the required extent.
In very cold temperatures outside, the heat is preserved by intensive constriction of skin
blood vessels and also extra heat is generated if necessary by involuntary contraction of
muscles manifest as shivering.
Above 1000
F the condition is called fever which is commonly seen associated with
infections, medicines (drug fever), in women mid menstrual cycle or injury (trauma). If the
temperature rises above 390
C especially in children, there can be serious consequences on

22
brain cells resulting in convulsions. At 400
C and more the proteins of the cells can coagulate
resulting sometimes in an irreversible damage.
If outside temperature falls rapidly below freezing as on exposure for long time to freezing
temperatures or on immersion or drowning in freezing sea waters, the body tends to loose
heat rapidly, what is called Hypothermia.
There are 3 grades of it. Mild (350
C - 320
C); Moderate (320
C - 280
C) and severe (280
C and
below) and can once again be rapidly fatal as heart tends to fibrillate and stop. The body
temperatures can be measured in a variety of ways. Orally, rectally (called core temperature),
in armpit (Axillary), from ear (Tympanic) and from skin. Ref Vital Signs (Body Temperature,
Pulse Rate, Respiration Rate, Blood Pressure)
http://www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=85,P00866
2.11 Exercise Lactate:
The end product of carbohydrate metabolism in the body results in the production of energy
from Glucose with also production of energy from glucose with also product of lactic acid,
that dissociates to give rise to H+ ions, and combination of remaining compound with Na+
and K+ ions to produce salt called lactate. It was initially believed that the end product of
Glycolytic pathway was pyruvic acid which under anaerobic conditions (insufficient oxygen
during exercise) converted to lactic acid thus caused increase in lactate in blood and muscles
resulting in fatigue. The importance was naturally related to sports medicine. With progress
in research over the last 30 - 35 years the views are changing and today it is held that it is the
excess accumulation of H+ from lactic acidosis, rather than excess production of lactate itself
which is the cause of muscle fatigue and tiredness and therefore lactate is not the foe but a
friend of athletes. More research is therefore still needed. The normal range of blood lactate
is 0.5 to 2.2 millimoles/l and in exercise or sports this is thought to rise rapidly as clearance
cannot keep pace with the event and complete exhaustion occurs between 20 - 25 mmoles/l.
Ref: Lactic Acid & Blood Lactate; http://www.sport-fitness-advisor.com/lactic-acid.html
2.12 Body Mass Index (BMI)
Body mass index is a useful measure to indicate whether a person has a healthy weight
compared to her/his height. For adults the ideal BMI varies between 18.5 - 24.5 range and
above this depending on the level (25 - 29.5 - considered overweight) and (30.0 - 39.9) obese.
Above 40 person is said to be very obese. In children the BMI is interpreted differently. This
index gives an overall idea of one's health and the amount of correction required to put it
right e.g. overweight BMI makes a person more prone to conditions such as heart disease,
strokes, Diabetes, some cancers, high blood pressure and kidney disease.
Underweight BMI on the other hand (i.e. less than 18.5) manifest also with affection of health
in the form of absent periods in women (Amenorrhoea), brittle bones, iron deficiency
anaemia etc. While taking into account BMI one also needs to take into consideration other
things such as disposition (athletic, ethnicity etc.)

23
Ref: What is the body mass index (BMI) - Health Questions - NHS Choices
http://www.nhs.uk/chq/Pages/3215.aspx?CategoryID=51
2.13 Blood Alcohol:
Alcohol is chemically known as C2H5OH. It is a liquid that is commonly consumed all over
the world as a social drink. It is the only substance apart from water, which is rapidly
absorbed at the level of stomach. Hence it raises the level in the blood rapidly producing
initial stimulation of central nervous system with sense of well-being and euphoria. However
in larger doses it is depressant and impairs judgement. The effects depend upon amount of
and concentration of alcohol consumed, the rapidity of intake prior food consumption, stress
level, metabolism, apart from age, sex and weight.
As alcohol impairs judgement, drink driving is very dangerous and can lead to serious road
traffic accidents. Hence there are strict alcohol limits for drivers in civilised world and heavy
& serious penalties for exceeding the permitted limits. The legal limits by government in UK
to drivers is 35 micrograms of alcohol/ 100ml of breathe, 80mg/100ml blood and
107mg/100ml of urine. Routine police patrol checks with breathalyser test and if necessary
blood checks by Police Doctor are in place.
Apart from this there are readymade charts to assess Blood Alcohol Concentration (BAC)for
men & women which give approximate blood alcohol percentage depending on number of
drinks, for legal purposes 5 drinks are considered intoxicating and 10 & above death is
possible and there are criminal penalties. Liver detoxifies alcohol and hence in chronic
drinkers cirrhosis of liver is the end result.
Ref: BAC Charts http//www.brad21.org/bac_charts.html; the drink drive limit - GOV.UK;
https://www.gov.uk/drink-drive-limit
2.14 K+ (Potassium):
Potassium is an important, in fact vital component of intracellular compartment just as Na+
(sodium) is in the extracellular compartment. It is a mineral which is normally found in
varying amounts in all types of foods; Potassium is an electrolyte just as Na+
and Ca++
, Cl-
,
Magnesium++
are, as all these ions help to conduct electrical charges in the body. Just as
others body can only function within an in narrow range of this electrolyte and thus possesses
elaborate system of checks to maintain its homeostasis. If despite these checks, the
potassium levels go too high or too low; then it leads to complete shutdown of Nervous &
Cardiac systems, this of course is life threatening
As mentioned above regards external food resources; the green and leafy vegetables such as
spinach, crimini mushrooms, tomatoes, Vegetables especially green varieties are richest
source of potassium. Potassium and sodium exist in partnership. The dietary approach
should be to maintain good balance in Potassium & Sodium in order to maintain a good heart
and kidney health. Apart from Bananas, yoghurt and eggs are good dietary sources of

24
potassium. Normally the body maintains, along with diet a good balance of Na+
& K+
electrolytes which helps to maintain Heart and Kidneys in good health. Conversely there is
no worry about toxicity of this ion so long as these organs are functioning well. It is in heart
failure or kidney disease that one needs to take care to prevent toxicity. It has been argued
that the diet rich in potassium helps to reduce risk of kidney stones as it prevents precipitation
of calcium in urinary system. Diarrhoea, vomiting, fluid imbalance are a common cause of
deficiency of this ion especially in Afro Asian countries with resultant morbidity and
mortality.
Ref: TheWorld'sHealthiestFoods;
http://www.whfoods.com/genpage.php?pfriendly=1&tname=nutrient&dbid=90
2.15 Drugs of Abuse:
It is important to realise the importance and seriousness of these drugs as these drugs cause
disruption to the process of normal communication between brain cells. Normally the
information collected from eyes, ears and other sensory organs is transformed into an
information that is relayed from cell to cell to certain regions of brain which specialise in
processing this information and attaching meaning and memory to it. Inside the cells the
information travels in the form of electrical signals but at intercellular gap the transmission
occurs in the form of chemical signal with the help of specialised chemicals. The process is
known as neurotransmission and the specialised chemicals are called neurotransmitters.
The process is comparable to computers & their semiconductor system except that it is much
more complex in case of brain. The drugs of abuse as mentioned above, by disrupting this
normal process alter the way a person thinks, feels or behaves. The evidence points to
induction of two important factors of drug dependence and addiction which are the main
features of organic brain disease produced by these drugs. The common known or isolated
neurotransmitters are Dopamine, serotonin, Noradrenaline, Endorphins, Gamma amino
butyric acid (GABA) etc. The drugs of abuse act in various ways of mimicking, or by
interacting with molecular components of sending and receiving process, attaching to
receptors etc. Initially as the drug leaves the system the effects wear off; intoxication ends
and the person returns to normal in initial stages of experimentation with them. In chronic
cases permanent abnormalities set in neurotransmission resulting in dependency, withdrawal
symptoms, addiction etc. The research in the field has taken impetus from availability of
brain scans currently especially from Positron Emission Tomography (PET scan).
Ref: Impacts of Drugs on Neurotransmission; National Institute on Drug Abuse (NIDA)
http://www.drugabuse.gov/news-events/nida-notes/2007/10/impacts-drugs-neurotrans...

25
3 Opportunities for measurements of Health Tracker
Parameters/Indices/Markers:
Prioritized List
As stated above I shall now briefly discuss some of the common conditions in routine
practice encountered where these measurements are appropriate in fact vital
3.1 Diabetes Mellitus:
Figure 2 : Worldwide distribution of diabetes prevalence in 2005 and estimated
numbers for 2030 (adapted from WHO, 2004)
1. This is the condition of complex endocrine metabolic disorder that results from total or
partial lack of hormone Insulin. It produces chronic hyperglycaemia or excess sugar or
blood glucose. History records show that the Egyptians first mentioned about Diabetes
1500 BC. The Greek physician called Aretaeus (130 - 20CE) named this condition
Diabetes, meaning "flowing through" as he noted the condition caused symptoms of

26
excessive urination, much thirst and weight loss. More clear documentation of Diabetes
is credited to an Arab Physician Avicenna (980 - 1037 CE) who accurately described its
clinical features, progress and above all complications. The final solution was in great
research work and isolation of insulin by Canadian physicians in 1922 by Nobel
laureates Banting and Best (Ref: History Committee Institute of Biomedical Science;
London; March 2012).
The body needs Glucose supplied by carbohydrate metabolism constantly for the
production of energy but the level needs to be maintained constantly between 4 - 6
mmoles in order to maintain internal environment of homeostasis. The excess of glucose
can usually get glycated to Haemoglobin (CHbA1c) or excess may pass down the
kidneys in urinary tract in urine called Glycosuria. Normally body can utilise glucose by
muscles and other tissues when it is allowed to enter their cells by a hormone called
insulin mentioned above. It is produced by β cells of pancreas. The autoimmune
destruction of β cells or resistance to insulin utilisation results in Diabetes Mellitus.
There are normally 2 types of Diabetes:
Juvenile or Type I Insulin Dependent as seen in some children (due to autoimmune
destruction of β cells)
Type II which is much more common (95%) manifests in adults and elderly
(predominantly due to insulin resistance)
(Ref: Type 2 Diabetes; 2nd
Edition by Andrew Krentz and Bailey)
Type III category is added by WHO to accommodate Diabetic conditions which do not
fit into above 2 types. These conditions include diseases such as endocrinopathies,
gestational Diabetes, Genetic defects etc. (Turner & Wass; 2002)
At present condition of Diabetic Disease is ubiquitous, worldwide. The condition is as
of today lifelong and incurable. As much of epidemiology and cost burdens are covered
under sections of disease prevalence and incidence as well as burden of disease and cost
effectiveness (the sections that follow) I avoid further repetition of discussion here. One
would however like to mention some important points. The most important in Diabetes
is careful monitoring and maintenance of blood glucose levels to near normal (110mg/dl
±25mg/dl) (Ref: Glucose monitoring; E. Wilkins & P. Atanosov: Med.Eng. Phys; 1996).
If glucose remains normal or at least near normal, then complications are avoidable and a
Diabetic can live an almost normal lifespan but control a must as said "Diabetes does not
go on holidays as you do"
The complications of Chronic Hyperglycaemia include macro vascular pathologies like
Coronary Heart Disease and Strokes and Microvascular entities like Nephropathy with
Renal failure. Retinopathy with blindness and Peripheral Neuropathy with attendant
ulcerations, infections etc. due to unrecognised injuries etc. Finally and most important
point, the causes of 2 types off Diabetes are different and so the treatment. Type 1

27
(Autoimmune) there is practically no indigenous insulin, complications are more due to
fluctuant blood sugars producing hyperglycaemic ketoacidosis or hypoglycaemic
episodes with attendant central nervous serious coma and convulsions. The treatment is
insulin. Either in divided doses or with open or closed loop administration. In type 2
the matter is insulin resistance (common type and in adults) and treatment is naturally
different. Diet and obesity control, exercise, oral hypoglycaemic or with insulin top-up.
Once again it brings out the importance of monitoring systems.
Above are a just a few but very important conditions in 20th
century leading into 21st
where it is almost self-explanatory the importance of health
tracker(parameter/indices/markers) with such conditions disease prevalence and
incidence as well burden of disease and cost effectiveness bring out their importance
more starkly. In this 21st
century with world population explosion of nearly 6.5 billion
and increasing, scarce resources, economic instability and austerity etc. The monitoring
- measurements need to be more accurate if we are still to continue to follow the
principle of "greatest good for greatest number of people within the available resources"
3.2 Infectious Diseases:
These are the diseases basically as name would suggest are diseases that cause infections
transmitted from human to human through environment (air droplet infection) or through
contaminated water or food or excreta or through a vector e.g. Insect bite or animal.
These diseases are caused by viruses, bacteria, fungi, parasites causing spread of disease.
Infectious diseases of animals are called Zoonotic disease which can cause disease in
human if transmitted. There is huge WHO list of these diseases which cannot be written
here but to enumerate some common import diseases and to get an idea it would suffice
to mention Leprosy, malaria, Tuberculosis, Dengue fever, Hepatitis (ABCE),
Poliomyelitis, measles, chickenpox, Small pox (now eliminated by worldwide
vaccination efforts by WHO), Influenza, Cholera, Gastroenteritis, meningococcal
meningitis, HIV etc.
There are normally three distinct stages of diseases of infectious nature:
Presymptomatic
Progression or stage of clinical disease &
Outcome or stage of diminished capacity.
In the presymptomatic stage of disease is not manifest but the person is affected and
may have some vague feelings such as anorexia, malaise, mild fever etc. this is called
prodromal stage where there is an incubation period between infection and its
manifestations. Stage 2 or progression (stage of manifest disease and depending on the
disease and organs affected have different signs e.g. fever (usually high, rash, cough and
expectoration, vomiting and diarrhoea, Jaundice, or affection of brain and muscles of
extremities as in Poliomyelitis, neck stiffness in meningitis.

28
Stage 3 or Stage of Diminished capacity or morbidity & unpleasant sequelae e.g.
Pneumonia with slow recovery, permanent damage to extremities e.g. in Polio, or
dehydration with cholera. The patient may recover from immunity, timely and correct
treatment or succumb to infection with resultant mortality. In the past there have been
regular epidemics of infectious disease worldwide due to lack of knowledge, medicines
and preventive vaccinations which caused high but preventable morbidity and mortality.
But thanks to WHO efforts as well as efforts at individual national levels a great relief
has been brought. Ref: Infectious Diseases http://www.mayoclinic.org/diseases-
conditions/infectious-diseases/basics/definition/con-20033534; Epidemiology
http://gwxy.sysu.edu.cn/lxbx/english/epidemiologic%20knowledge/Selected%20Disease
%20Concepts%20in%20Epidemiology/Natural.html
3.3 Malnutrition:
Malnutrition is a condition of inadequate supply of nutrients to the body. The condition
is usually due to dietary inadequacy. Malnutrition can be of under nutrition type or over
nutrition resulting in excess supply of nutrients and resultant obesity.
This obesity is a different topic by itself and not discussed here. It is the under nutrition
which is focussed on. The causes may be many, most important reduced mobility as
seen in elderly persons, or persons suffering from disease. The person's body may not be
able to absorb the adequate amounts of nutrients due to existing disease or may be due to
economic conditions as seen in lowly developed countries.
The malnutrition may manifest in the form of loss of weight commonly losing 5-10% of
body weight in 6 months, fatigue and tiredness or proneness to infections and anaemia.
It is more widespread than one can believe. For e.g. nearly 1 in 3 persons admitted to
care homes or hospitals in UK are malnourished. There are 3 million people in UK itself
that are malnourished let alone in the developing world. The improvements can be
obtained by dietary adequacy of nutrients, and in problem cases of feeding by using
nasogastric tubes to stomach or drips of nutrients.
Malnutrition http://www.nhs.uk/conditions/malnutrition/Pages/Introduction.aspx
3.4 Mental illness
I have defined the mental health in previous discussion as per the definition provided by
WHO. To mention in short, the importance lies ( as seen in incidence and prevalence)

29
the mental illness is rapidly increasing in populations all over the world and expected to
exceed other conditions, the commonest mental disorder being depression.
The mental illness is divided for simplicity into following categories:
Anxiety Disorders - where depending on its severity patients react to even simple or
trivial matters with extreme of fright or dread
Mood Disorders - depression, mania, bipolar disorders fall in this category and especially
depression the commonest mood disorder is due to circumstances he/she faces
Psychotic Disorders - this is seen in persons suffering from hallucinations, imagining
various voices or sounds or conditions which do not exists in reality. The other
symptoms are delusions
Impulse control and addiction disorders - where the persons are driven by their craving
for things or drugs and are driven impulsively without the normal control of rationality
Eating disorders- as seen in conditions of anorexia nervosa and bulimia where persons
have revulsions for food intake.
Personality disorders - where person's behavioural attitude is that of extreme
inflexibility, rigid and irrational rather than the flexibility which society would expect of
normal behaviour
Ref: Mental Health: Types of Mental Illness http://www.webmd.com/mental-
health/mental-health-types-illness
3.5 CHD (Coronary Heart Disease)
This is a condition that results that results from affection of coronary arteries, the arteries
that supply the blood to heart muscle. As heart is beating constantly in life it needs a
constant and steady blood supply. However the lining of these vessels can get rough
ends over a period of time by deposition excess cholesterol over the vascular endothelial
lining, Diabetes, Hypercholesterolemia (High Blood Cholesterol) heredity are common
causes and smoking is a precipitating factor. The deposition results in the formation of
waxy hard material called plaques which narrow the arteries producing starvation of
heart muscle especially during exercise manifest as chest pain called angina. The patient
may be relieved of symptoms by rest or added medications to dilute coronary arteries &
increase flow of adequate blood volume.
Sometimes these plaques can unfortunately rupture producing acute blockage to blood
flow starving heart of oxygen resulting in death of that part of the heart supplied by
particular branch of vessels. This is a medical emergency called acute coronary
syndrome, myocardial infarction or simply heart attack in lay terms.
Ref: Brief Overview of Coronary Artery Disease
http://heartdisease.about.com/cs/coronarydisease/a/CAD1.htm

30
3.6 Cancer
This is a conditions where cells in specific part or organ of the body begin to grow and
reproduce uncontrollably. These rapidly growing cells then invade and destroy
surrounding healthy parts of organs and tissues. The cancer cells begin in one part of the
body by progressively spread to other areas, a process called metastasis. The spread
occurs usually through continuity and by Lymphatic system as well as blood to much
distant areas. It is unfortunate that despite centuries of its known existence, of extensive
research, money spent on it and the amount of work put in, there is no solution to the
problem as we as yet do not know the exact cause for this abnormal change in growth
and formation of cancer cells in the first instance. It remains incurable to date and stamp
of death is synonymously associated with it by common man. However some factors
such as radiation, smoking etc. are known to be causative factors.
There are over 200 different types of cancers affecting body and some of the common
ones I have mentioned under the heading of Disease Prevalence and Incidence and thus
not repeated here. I should like to mention that cancer usually has an insidious onset and
in some cases it is quite advanced before coming to diagnosis. Hence if there are any
changes to body's normal processes such as bowel habits, occurrence of unexplained
bleeding or appearance of lump etc., then one needs to see his/her GP for consultation.
In early stages most cancers are curable in terms of 5 year survival rates. WHO records
show that cancer deaths reach the mark of 1.6million per year and every year millions
get diagnosed of it e.g. In UK alone in 2009 320467cases of cancer were diagnosed and
the commonest cancers found in UK affect Breast, Prostate, Lung, Bowel, Bladder and
Uterine (Cervical & Body) cancer.
Cancers of different organs and depending upon the stage at diagnosis apart from age
and sex, need different types of treatments. But generally speaking Chemotherapy,
Surgery, Radiation therapy form the main stay of treatment. Once again it is needless to
add that close follow up of patient is required in order not to miss recurrence.
Cancer - NHS Choices http://www.nhs.uk/conditions/cancer/Pages/Introduction.aspx
3.7 COAD (Chronic Obstructive Airway Disease)
As the name suggest it is a condition which results over period in obstruction to flow of
gases namely the exchange of Oxygen and carbon dioxide resulting chronic tissue
starvation for Oxygen and Accumulation of CO2 called carbon dioxide narcosis. This
condition usually affects middle and old ages and occur as a combination of Chronic
Bronchitis and Emphysema by constant irritation of Bronchi from irritants especially
tobacco nicotine; excessive secretion of mucus by airway cells lining and loss of ciliary
movement (fine hair like structures which line these cells and move to the mucous up).
There is also a loss of elasticity of lungs' sacs called alveoli.

31
The cumulative effect is collection of thick secretions, narrowing of passage and as
mentioned above obstruction to air flow and gaseous exchange. This conditions as said
above is particularly seen in Tobacco smokers which reduces their life expectancy
considerably Ref: Chronic obstructive pulmonary disease
http://www.nhs.uk/conditions/chronic-obstructive-pulmonary-
disease/Pages/Introduction.aspx.
4.1 Disease Prevalence and Incidence:
The prevalence of an illness or condition according to WHO definition "is the number of
individuals who have the condition at any moment in given time" WHO (2004)
http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
Anaemia, hearing loss and migraine are the 3 most prevalent conditions in the world.
The other prevalent conditions such as arthritis, asthma, intestinal worms, visual
problems, major depressive episodes, injuries and cardiovascular diseases add to the list
with various levels of severity and multiple disabilities that cause health problems. The
GBD (Global Burden of Disease) links the average loss of health to disease and injury
but prevalence data does not indicate it.
Ref:
WHO (2004)
WHO The top 10 causes of death; http://www.who.int/mediacentre/factsheets/fs310/en/
WHO Burden of disease and cost-effectiveness estimates
http://www.who.int/water_sanitation_health/diseases/burden/en/
WHO About the Global Burden of Disease (GBD) project
http://www.who.int/healthinfo/global_burden_disease/about/en
Incidence and prevalence of chronic disease (MPKB)
Http: //mpkb.org/home/pathogenesis/epidemiology`

32
WHO (2004)http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
Accessed on 30/5/2014
Table: 1: Prevalence (millions) of selected conditions by WHO region, 2004
The incidence of the condition is a number of new cases in a period of time - usually one
year. The diarrhoea disease is the most common cause of illness worldwide. The
incidence includes low, middle & high income countries. Pneumonia and other lower
respiratory tract infections are the 2nd
most common cause of illness globally. Other
illnesses such as Upper Respiratory tract infections (including common cold) and allergic
rhinitis (Hay fever) form the list.
Ref:

33
WHO (2004)
WHO The top 10 causes of death; http://www.who.int/mediacentre/factsheets/fs310/en/
The incidence of the condition "is the number of new cases in a period of time - usually 1
year" once again as per the WHO definition. The diarrhoeal disease is still the most
common cause of illness worldwide (indicating water - sanitation problem). The second
highest include lower respiratory tract conditions including Pneumonia and incidentally
includes low as well as middle and high income societies. Other infections such as upper
respiratory tract infections (including common cold) and hay fever add to the list
WHO(2004)
http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/.

34
Table: 2: Incidence (millions) of selected conditions by WHO region, 2004 WHO
(2004) http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
Cancer incidence is increasing and is relatively taking upper head globally. In 2004 11.4
million people were diagnosed in the whole world of cancer. Generally cancer incidence is
higher in high and middle income societies. Uterine cervical cancer is the only exception,
incidence of which is higher much more in African and South East Asian societies. Lung
cancer incidence is highest globally followed by Prostate, Breast, Colon and Rectum and
Stomach cancers. Prostate cancer affects more elderly population than younger males and it
is to be noted that the pattern of incidence of diseases and mortality and morbidity related to

35
They is changing world wide due to better health facilities. I mention here the list of Top 10
contenders of mortality (death|) between 2000 and 2012 worldwide to bring out this point.
i. Ischaemic Heart disease
ii. Stroke
iii.COPD
iv. Lower respiratory tract infections e.g. Pneumonia
v. Trachea Bronchus & Lung Cancers
vi. HIV AIDS
vii. Diarrhoeal diseases
viii. Diabetes Mellitus
ix. Road Injury
x. Hypertension
Figure 3: The 10 leading causes of death in the world; WHO (2014)
http://www.who.int/mediacentre/factsheets/fs310/en/ Accessed on 30/5/2014
WHO (2004)

36
WHO The top10 causes of death;
http://www.who.int/mediacentre/factsheets/fs310/en/
Figure 4: The 10 leading causes of death in the world by percentage; WHO
(2014) http://www.who.int/mediacentre/factsheets/fs310/en/ Accessed on 30/5/2014
Its starkly brings out the differences in 20th
and 21st
century. Diarrhoea is much lower in rank
now though still in top 10 causes. HIV and AIDS have decreased but just slightly from 1.7
million to 1.5million. But chronic diseases particularly Diabetes is raising the head
worldwide.

37
It however makes most interesting reading to see the list of top 10 causes of death as tallies
were done in 1900 and 1997 ( almost century apart ) in USA. In 1900 in USA the top 10
were:
i. Tuberculosis
ii. Pneumonia
iii.Diarrhoea
iv. Heart Disease
v. Liver Disease
vi. Injuries
vii. Stroke
viii. Cancer
ix. Bronchitis
x. Diphtheria
In 1997 in USA top 10 tally shows a distinct change
i. Heart Disease
ii. Cancer
iii.Stroke
iv. Chronic Lung Disease
v. Unintentional injuries
vi. Pneumonia/Influenza
vii. Diabetes
viii. Suicide
ix. Chronic Kidney Disease
x. Chronic Liver Disease

38
Figure 5: The ten leading causes of death in the United States in 1900 and
1997; 2014 (MPKB) The Marshall Protocol Knowledge Base;
http://mpkb.org/home/pathogenesis/epidemiology Accessed on 30/5/2014
This is an interesting reading. One can see that acute infections like Diphtheria and
thank god chronic infections like Tuberculosis have disappeared from the list
altogether but unfortunately their place has been replaced by more chronic conditions
particularly Diabetes Mellitus which produces complications and adds to morbidity
and mortality. European pattern appears to be similar, cardiac, strokes, cancer and
chronic lung disease amongst the top 10 contenders. Ref:
WHO
(2004)http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
WHOThetop10causes of death; http://www.who.int/mediacentre/factsheets/fs310/en/
Incidence and prevalence of chronic disease (MPKB) http:
//mpkb.org/home/pathogenesis/epidemiology`

39
Table: 3: Incidence (millions) of selected conditions by WHO region, 2004 WHO
(2004) http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/
The current prevalence of chronic disease in USA throws some light. In 2000 approximately
125 million Americans (45% of population) had chronic conditions. 61million (21%) had
multiple chronic conditions. Even in children chronic health conditions in USA showed
distinct rise from 12.8% in 1994 to 26.6% in 2006 particularly for Asthma, Obesity,
Behavioural and Learning problems (JAMA 2010 - Ref)
Adults with the multiple chronic conditions are the major users of healthcare services at all
adult ages and account for more than 2/3 of healthcare spending (Ref).

40
A Dutch (European) analysis brings out the same message. The prevalence of chronic
diseases showed doubling between 1985 and 2005 with proportion of patients with 4 or more
chronic diseases increased by 300%. There is a further projected increase as also shown by
world report (Ref)
In 2002 leading chronic diseases, cardiovascular, cancer, chronic respiratory disease and
Diabetes caused 29 million death worldwide and annual mortality is expected to go up in real
numbers in relation to injuries and infections such as Polio, Rubella, and TB etc. WHO itself
described Diabetes as "world epidemic "with projected increase from 194 million to more
than 330 million by 2025. In fact CDC (Centres for Disease Control) projected to over 500
million in the next 25 years which appears more realistic realising the trend.
One can only imagine the health cost burden due to this and related co morbidities as well as
moderate to severe disabilities. A paper in 2010 by Boyle predicts that 1/3 of US population
will have Diabetes by 2050. It has also been predicted that by 2020 Atherosclerosis will be
the primary cause of death in the world, a truly shocking situation. Psychiatric disorders are
also on the increase and are expected to take over 1st
place within the next few years. Once
again one has to imagine the cost burden of the conditions, their chronicity and problems and
stress levels in the society.
4.2 Burden of Disease and Cost Effectiveness Estimates:
As mentioned in above discussion poor sanitation and water quality still keep haunting us as
a threat to human health despite commendable work by WHO. The diarrhoeal disease has
much gone down in rank as a cause of mortality but it still accounts for estimated 4.1% of
TOTAL DALY (Disability Adjusted Life Year - use to quantify burden of disease from
mortality and morbidity ) and is responsible for deaths of 1.8 million annually as per the
estimate in 2004. Today in 2012 it is estimated at 1.5 million. Unfortunately Diabetes
mellitus has also shown a similar mortality of 1.5 million and increase worldwide. Naturally
expected increase in DALY. Nearly 88% of burden is attributable still to precarious and
unsafe water supply, hygiene and sanitation, and concentrated on children from developing
countries. (Ref)
WHO has already estimated the cost effectiveness of health benefits and other additional
benefits through better sanitation and safe portable water supply and other interventions for
each of the 14 sub regions it has divided the countries in two.
It is currently trying to estimate National level burdens of water related diseases and cost
benefits of safe water and sanitation services. Well, coincidently direct costs of Diabetes
Mellitus are estimated to be 9% of NHS budget and 14% of US Healthcare Budget (Type 2
Diabetes by Andrew Krentz & Bailey - 2nd
Edition).
This shows the urgent needs to put in equally more efforts in preventive, social and
management aspects of this disease Diabetes and hence my intention to concentrate in this
field.

41
4.3 Effectiveness of monitoring:
As the old adage in management goes "if you want to improve something, start by measuring
it or you won't see how to make a difference". In today's 21st
century "world is a global
village" concept is aptly applicable, particularly because of computer science application and
fast modes of communication and transportation. The movement of people has increased
from one corner of the world to another and thus monitoring of health and disease has
become particularly important especially Infectious or communicable diseases and water
borne diseases and air pollution. WHO has been doing a commendable work in this field of
monitoring and particularly checking the effectiveness of these methods of monitoring
adopted e.g. international efforts of developing mass vaccination programmes in case of some
dreaded infections viral infectious disease, such as small pox, polio, influenza has led to
complete irradiation or marked reduction in the number of cases. Surge of small pox has
been eradicated from this earth and in India now Polio has been eradicated so has been in
developed world which is commendable.
Increasing improvement in water sanitation has resulted in Diarrhoea shifting its position
from amongst the first top ten killers (from 1st
to 6th
position) as would be self-explanatory
from figures on previous pages. As also mentioned previously; monitoring list of top 10
contenders in USA in 1900 &1997 brings this out very starkly. Diphtheria has disappeared
from the list and place is taken by more chronic conditions especially Diabetes & Chronic
Lung Diseases e.g. COAD. Hence the importance of measuring effectiveness of monitoring,
so as also to fit in with changing incident pattern of diseases.
The truth about above statement is particularly brought out by the fact of more personalised
medicine trend in current age. With advances in Enzymatic Electrochemistry,
nanotechnology, physics etc.; there has been nearly an explosion in availability of cheap
enough gadgets, mostly portable in these days of consumer technology. As per the first
national survey on Self Tracking done by Pew Internet (2012) Ref: How self-monitoring is
transforming health - Medical News Today
http://wwwmedicalnewstoday.com/articles/264784.php 7 out of 10 adults Track one at least
one health indicator (60% track weight, diet or exercise and 33% track health symptoms e.g.
Blood Sugar, Blood pressure, sleep pattern, headaches, Heart rate etc.) and it is estimated that
in few years there would be nearly 170 million wireless gadgets around the world doing self-
health tracking. This trend in Self Health Tracking is "the biggest shake up in the history of
medicine" according to one of the leading Physicians Eric Topol.
The worry about the faulty monitoring either by gadget or an individual is being overcome by
technology developed by Professor Lionel Tarrasenko, at University of Oxford and Director
of Oxe Health in UK's Biomedical Engineering. I believe this clearly brings out the
importance of measuring effectiveness of monitoring if we are to tackle present day Top 10
killers on previous pages particularly Diabetes, Coronary Heart Disease, Strokes COAD etc.

42
Above parameters/Indices are very useful for health tracking or monitoring which should
now bring us to mentioning salient points of our this specific exercise in terms of aims &
objectives
5
5.1 Aims:
Our aim is to identify a Health Tracker Parameter & to develop a preliminary device to
monitor that parameter.
Having gone through the important common parameter/indices/markers I have discussed
above, I aim to select the parameter of blood glucose. In my further discussion I shall
mention the reasons for doing so, under the heading of Rationalisation. In this section I
mention it to clarify the thoughts. Similarly I should like to state that the device in mind to
monitor this parameter is a biosensor (Glucose monitor). This too is more discussed and
reasoned under the heading of Rationalisation and also in Biosensor.
5.2 Objectives
Identify parameters linked to well-being prioritise parameter list
Identify existing methods to monitor these
Design Prototype device
Test device & propose optimisation/further work
6
6.1 Monitoring Systems:
As mentioned above under the heading of effectiveness of monitoring an important old adage
in management that " if you want to improve something then start measuring or monitoring it
otherwise you won't see how to make a difference". I find this adage entirely appropriate and
thus re mention it. Latter half of last century and the beginning of current century has seen
considerable advances particularly in the fields of electrochemistry especially enzyme
chemistry as well as advances in physics (optical physics) in particular and in the field of
nanotechnology. The trend of having everything big is giving way to miniaturisation. The
things are thus becoming more cost effective and efficient leading to better measuring and
monitoring with the advent of age of sensors. A sensor is a device as the name suggest
senses or detects any change happening. There are usually 4 types of sensor systems in
common use currently:
1. Physiological sensors

43
2. Chemical sensors
3. Remote sensors
4. Biosensors
6.1.1 Physiological sensors
This is a system of sensors which help to measure or record some of the physiological indices
of stress, emotions etc. when a person is subjected to such exposures of psychological stress
and additive substances in natural environments and thus quantify them. Such a system of
sensors has been developed by team of scientists at Ohio State University arranged in the
form of wearable chest band. This provides steady measurements, with the use of two lead
ECG (Heart Rate and its pattern); Respiratory rate (with plethismography); skin/body
temperature (with surface probe thermistor), Skin conductance Response (SCR), motion
sensing using three axes accelerometer. All the sensors with their bio-amplifiers and signal
conditioning circuitry are assembled into two wireless motes connected to smart phones for
computer assessment Autosense: A Wireless Sensor System to Quantify Personal Exposures
to Psychosocial Stress and Addictive Substances in Natural Environments; Physiological
Sensors; https://sites.google.com/site/autosenseproject/research/chestband.
There is another connecting bridge mote which provides SD (Store Data) Card in case of
problems with smart phones or batteries to make the system fail safe about records.
Figure: 6 Mote 1 Form Factor; Sensor: ECG, Temperature, GSR, Accelerometer;
Autosense: A Wireless Sensor System to Quantify Personal Exposures to Psychosocial Stress
and Addictive Substances in Natural Environments;
https://sites.google.com/site/autosenseproject/research/chestband; Accessed on 17/5/2014

44
Figure: 7 Mote 2: Form Factor; Sensor: Respiratory Inductive Plethysmograph
(RIP); Autosense: A Wireless Sensor System to Quantify Personal Exposures to
Psychosocial Stress and Addictive Substances in Natural Environments;
https://sites.google.com/site/autosenseproject/research/chestband; Accessed on 17/5/2014
Figure 8: Bridge Mote Form Factor; Autosense: A Wireless Sensor System to Quantify
Personal Exposures to Psychosocial Stress and Addictive Substances in Natural
Environments; https://sites.google.com/site/autosenseproject/research/chestband; Accessed
on 17/5/2014

45
Figure 9 : End - to - End System; Autosense: A Wireless Sensor System to Quantify
Personal Exposures to Psychosocial Stress and Addictive Substances in Natural
on 17/5/2014
Figure 10: Signal captured from the Autosense system on a laptop appears below.
Red is respiration and green is the ECG; Autosense: A Wireless Sensor System to
Quantify Personal Exposures to Psychosocial Stress and Addictive Substances in Natural
on 17/5/2014
The signals from the system are visualised on laptop with continuous analysis of
Physiological changes for nearly a week at present. Such physiological sensors would be
quite useful especially in the field of medicine.
6.2 Chemical sensors:
A chemical sensor is a device that transforms chemical information (e.g.: composition of
substance under analysis, chemical activity or ions etc.) into a signal that can be analysed.
The information comes from physical property of analyte or by its chemical reaction. These
sensors usually have two components connected in series, a chemical molecule recognition
system called receptor, the other being a physicochemical Transducer. The receptor
interacts with molecules of analyte under investigation. This primary signal may be in
electrochemical, optical, mass, or thermal (heat) form. The transducer picks up the signal, it
is amplified by connected amplifiers and the final signal in the form of electrical current is

46
helpful to measure the concentration etc. (quantification) of system under investigation being
proportional. Chemical sensors have wide variety of applications such as Home Safety,
medical fields, Environmental (eg.to see level of pollution etc.) CHEMICAL SENSORS -
Nano-Bio Spectroscopy Group; nano-bio.ehu.es/files/chemical_sensors1.doc_definitivo.pdf
Figure 11: Composition of Chemical Sensor; CHEMICAL SENSORS - Nano-Bio
Spectroscopy Group; nano-bio.ehu.es/files/chemical_sensors1.doc_definitivo.pdf Accessed
on 17/5/2014
Examples of some of the chemical sensors seen in routine use are e.g. CO (Carbon
Monoxide) detectors, blood glucose detectors, Home Pregnancy tests kits etc. Just to
mention out of interest an insect (mosquito) possess variety of sensors in its antennas. One of
which is a chemical sensor which detects Carbon Dioxide (CO2) & Lactic acid produced in
breathe of mammals up to as long as a distance as 36 meters and this therefore results in
mosquito bites.
Nanotechnology has given a considerable boost to the use of chemical sensors in various
fields such as Communications, Transportation, medicine, safety and National security
CHEMICAL SENSORS - Nano-Bio Spectroscopy Group; nano-
bio.ehu.es/files/chemical_sensors1.doc_definitivo.pdf.
6.3 Remote Sensors:
These sensors gain information about objects or areas from a distance e.g. by means of
aircraft or satellites on which the sensors are fitted. The data collection is done with the help
of detection of energy reflected from earth, these sensors fall in 2 categories active or passive.

47
The passive sensors react to external stimuli. Recording the radiation reflected from the
earth's surface, normally from sun and hence can be used to collect the data only during the
daylight hours. Active sensors on the other hand use the internal stimuli to collect data about
earth e.g. by using laser beam to project by satellite etc. onto earth's surface and measure the
time it takes to reflect back to its sensor.
Remote sensing finds its applications in different range of fields including coastal, oceanic,
hazard assessment and Natural resource management such as wild life habitat &
environment.
Figure 12: A LIDAR (Light Detection and Ranging) image created with data collected
by NOAA's National Geodetic Service. March 20, 2014
http://oceanservice.noaa.gov/facts/remotesensing.html; Accessed on 17/5/2014
6.4
6.4.1 Biosensors:
A biosensor is an analytical device that incorporates a biological sensing element and
produces a specific response which can once again be converted with assembly of transducers
and amplifiers into a measurable current and thus quantify the concentration of analyte. With
progress in Electrochemistry and simultaneously in Nanotechnology the biosensors mostly
exploit the sensitivity and specificity of enzymes but other biological systems e.g. Antigen -
Antibody reaction, ligand binding and whole cell metabolism etc. are used.

48
6.4.2 MARKET & APPLICATIONS:
The field of Biosensors is rapidly expanding, currently at the rate of 60% growth per year. It
has received major impetus coming from healthcare system or industry. E.g. approximately
6% of the western world population is diabetic and this number is rapidly growing all over
the world as discussed further under rationalisation. This population would benefit
immensely from availability of rapid, simple and accurate measurement of Blood Glucose
with a biosensor device which should be inexpensive, useable by common man. Hence the
expansion has had to be two pronged, one being such small portable glucometers for public
use as personalised medicine effectively decentralising the pathology laboratory which
otherwise uses high throughput expensive equipment.
Biosensors find wide variety of applications including in:
a) Medicine (mainly in glucose monitoring in Diabetes which is the major share).
Pharmaceuticals (drug discovery etc.),
b) other health related parameters measurement (e.g. cholesterol estimation)
c) Food and processing control (determination of drug residues such as growth
promoters etc.),
d) environmental monitoring( e.g. pollution, detection such as pesticides, heavy metal
contaminants of river waters),
e) defence and security(e.g. detection of airborne bacteria in bioterrorists activities)
The current estimated market is $13 Billion, much of (30%) is driven by Medical
Diagnostics particularly in Diabetes as mentioned already, the trend being towards
personalised medicine. The market currently utilising only 0.1% capacity with a
huge scope for expansion. (Ref Biosensors: sense and sensibility; Anthony P. F.
Turner;Chem. Soc. Rev, 2013; 42, Pages 3175-3648.)(Enzyme Technology; what are
Biosensors? http://www1.1sbu.ac.uk/water/enztech/biosensors.html)
6.4.3 The Basic Components of Biosensors:
1. Biological recognition element
2. Transducer
3. Amplifier
4. Microprocessor with display unit

49
Figure13 : Schematic diagram showing the main components of a biosensor. The
biocatalyst (a) converts the substrate to product. This reaction is determined by the transducer
(b) which converts it to an electrical signal. The output from the transducer is amplified (c),
processed (d) and displayed (e). Enzyme Technology (2012) what are Biosensors?
http://www1.lsbu.ac.uk/water/enztech/biosensors.html; Accessed on 17/5/2014
Figure 14 :Working principles of a biosensor
Figure 15 : Glucose Detector

50
6.4.4 Requirements of Biosensors
A successful biosensor needs to possess certain beneficial features. To enumerate:
i. It should have demand ( this can be met as seen above)
ii. It should have a Biocatalyst under normal conditions of storage and be specific
iii. As far as manageable, the reaction produced in the sensor analysis should be
independent of physical parameters such as temperature etc.
iv. In case of invasive monitoring it should not be prone to fouling and be very tiny, non-
antigenic and sterilisable.
v. The response needs to be precise, accurate and reproducible
vi. Should have a good portability, cost effectiveness (cheap) and useable by common
person
(Enzyme Technology; what are Biosensors?
http://www1.1sbu.ac.uk/water/enztech/biosensors.html)
The biological recognition element is also called bio receptor and can be in many forms but
the commonest bio receptor use:
a) Enzymes - though they are costly, are highly selective and specific and above all
sensitive in their action. As enzymes do not get used or destroyed in the reaction but
only catalyse it, it is reusable many times before it loses its sensitivity. The problem
is with stability. However reusability as well as reproducibility of results makes it
affordable and attractive element. Other bio receptors used are:
b) Cells - they remain attached to the surface, remain active for a long time, and are
reproducible and reusable.
c) Antigen - antibody reaction - specific binding capacity of antibodies to certain
corresponding antigen is made use of in this form of biosensor. The binding event is
recognised with the use of tracing elements such as enzymes or fluorescent molecules
which produces a signal. The sensor is immunosensor.
d) Organelles - these are independent functioning units of cells with their enzymes to
perform those functions. Commonly used organelles include chloroplasts,
mitochondria (used for detection of calcium concentration of given medium) and
lysozymes.

51
6.4.5 Transducer/ Bio transducer:
This is a highly important unit of biosensor. It is the physicochemical change
recogniser and transductor (convertor) of biological signal produced (not quantifiable)
into a quantifiable electric current or voltage (in potentiometers). Biological
recognition element and Bio transducers are the biological components of biosensors.
The remaining three namely amplifier, microprocessor and display unit are electrical
components of the sensor and mostly are assembled together and many a time a more
costlier part of the system.
6.4.6 Functioning of Biosensor:
The biological recognition element reacts with the specific analyte that an analyst is
interested in. The biological signal produced by the reaction is picked up and
converted into quantifiable unit namely the electric current. The generated current is
amplified by amplifier with the suppression of noise or interference. Processed by
microprocessor this analogue signal is converted to digital signal finally to be
displayed by the display unit, as concentration of analyte as the produced electrical
current is proportional to the concentration (Enzyme Technology; what are
Biosensors? http://www1.1sbu.ac.uk/water/enztech/biosensors.html).
6.4.7 Classification of Biosensors:
The biosensors can be classified based on its transduction or detection element or
alternatively as per by its biological recognition element.
Classification by detection/ transduction:
This would include 3 electrochemical methods namely:
 Amperometric (using movement of electrons produced in redox
reaction)
 Potentiometric (changes in the distribution of charges producing
electric potential)
 Conductometric
 Others such as Optical, Acoustic and colorimetric (measuring heat
output of the reaction). With advances of optical physics the optical

52
sensor systems may be based on surface Plasmon response (SPR) or
merely changes of absorbance or fluorescence.
 Piezoelectric (where effects due to mass of reactants or products is
measured). Piezoelectric element is incorporated in the biosensor in
the form of crystal and binding of analyte changes the resonance
frequency which gives binding signal.
Classification by Biological Recognition Element:
Classification on this basis can be further subdivided into 2 categories:
a) Bio catalytic recognition
b) Bio affinity recognition
a) Bio catalytic recognition - in this mechanism of sensors either an enzyme, a whole
cell, cell organelles or biomimetic material or tissue as discussed above are
immobilized on the transducer as a biological compound or recognition element.
b) Bio affinity recognition - the recognition element is DNA and RNA based or antigen
antibody based ( immunosensors - see above) as well as can be receptor/agonists/
antagonist biosensor using membrane and capture configuration
DNA/RNA methods employ nucleic acids interactions recognition is based on principle
of complimentary base pairing and the sensors are called genosensors.
Developments in Nanotechnology has boosted the field of Biosensors with
measurements to molecular and atomic levels.
6.5 Glucose Biosensors:
Having discussed Biosensors it is now appropriate to discuss glucose Biosensors in
particular, since in my aims and objectives I have clearly mentioned my choice is to track a
health tracker parameter - blood glucose.
Glucose Biosensors though well-known and established as important health tracker parameter
in diabetics for testing as point of care (POC) or home and personalised medicine, also has
many other biotechnological, food & beverages, pharmaceutical industrial as well as

53
chemical industrial applications(Banker et al; 2009). It makes one understand their
importance
6.5.1 A brief historical perspective of glucose sensing
During mediaeval times attempts were made to diagnose diseases by examination of urine for
appearance, colour, sediment and even taste. In early 19th century glucose was identified in
urine as the sugar present in Diabetics later corroborated in 1838 by George Rees, from Guys
Hospital in London who isolated excess sugar in blood OD Diabetics. Stanley Benedict
devised a test in 1908 for urinary monitoring of sugar which was used for next 50 years 1970
- 1980s were years Anton Clemens at Ames developed quantitative blood glucose meters
developed by Life scan in 1980 in UK (1980 - 90) saw miniaturisation of glucose meters.
The choice slowly changed to Biosensor with enzyme chemistry with advances in
Electrochemistry with advances in Electrochemistry. The first glucose Biosensor system
ExacTech was launched by Medi sense in 1987 using enzyme electrode strips developed in
UK by Cranfield University & Oxford University (History Committee, IBMS, London;
March 2012). 1990 - 2000 saw increase in production of enzyme technology based glucose
biosensors as well as ISF continuous glucose monitoring. Abbott Labs, Bayer, Roche &
Life scan were the 4 companies dominating in the production of glucose meters totally
capturing 80% of world market. By 2000 the Reflectance technology based glucose meters
had become obsolete. (Rich Mendoza 1999).
6.5.2 Generations of Biosensors
Over the past 40 years various advances have taken place in the techniques and designs of
glucose sensors production. Depending on this the sensors could be divided into 3
generations but in order to realise the monitoring of diabetes control one needs to understand
how bio electrodes function. The figure below shows the working principle of Biosensors
along with figure above. The bio electrodes mostly use enzymes, the commonest being
glucose oxidase (GOx). The first glucose electrode used enzyme GOx entrapped over
oxygen electrode using a semi permeable dialysis membrane. This is the first bio electrode
and all biosensors are based on this original glucose enzyme electrode. The measurements
based here were based on O2 consumption by enzyme catalytic reaction
Glucose + Oxygen →GOx Gluconic acid + H2O2
Since then attempts in various forms have been made to improve electron transfer from active
site of Go to the electrode and to reduce the transfer distance.

54
6.5.3 First Generation Glucose Biosensors
This generation Biosensors relied on use of natural O2 cosubstrates production and detection
of H2O2. The electrons are transferred here from glucose to electrode in 2 steps:
Step 1: Reduction in Flavin group in the enzyme (FAD) to reduced form of enzyme (FADH2)
GOx (FAD) +Glucose →GOx (FADH2) +Gluconic Lactone
Step 2: re oxidation of Flavin by oxygen to give back re oxidised form of enzyme GOx
(FADH2) +O2 →GOx (FAD) +H2O2
Here the measurement of H2O2 produced are done using Pt (Platinum) electrode and
entrapped GOx between inner cellulose Acetate membrane internally (for anti-interference)
and outer biocompatible membrane. The problem with this generation of sensors is
limitation of oxygen diffusion to enzyme.
6.5.4 2nd Generation Glucose Biosensors
These 2nd generation sensors made use of mediators (non physiological synthetic) as electron
acceptors from redox centre of enzyme to electrode. Enzyme wiring was used to improve
the contact and also to get over problem of oxygen diffusion by use of mediators.
This involves direct transfer of electrons from glucose or analyte to electrode via active site
of enzyme with the total elimination of mediators. This therefore gives rise to high
selectivity (Malhotra & Turner 2003).
6.6
6.6.1 Problems to surmount in Glucose Biosensors
There are two main problems in the Glucose Biosensors which need to be carefully
overcome, one is to get correct reliable blood glucose readings, on which the dosage of
medication in the patient depends and there have been instances in the past with false
readings leading to wrong dosages of insulin heading to death. Hence importance of
reliability. The problems are mainly the two interference and fouling. Interferences can be
enzyme interferences or electrode interferences.

55
6.6.2 Enzyme Interferences
As mentioned in the 2nd generation Glucose sensors many manufacturers used glucose
dehydrogenase (GDH) instead of good old glucose oxidase (GOx). This obviously needed
cofactors such as FAD (Flavin Adenine Dinucleotide); PQQ (Pyrroloquinone Quinoline - see
reaction under 2nd generation sensors and NAD (Nicotine Adenine Dinucleotide). However
due to problem of instability apart from main concern of non-selectivity with cross linkage to
other sugars such as maltose, galactose and Xylase producing interference and unreliability
of results, the manufacturers had to stop GDH - PQQ and switch over to GDH - FAD
combination. Hence these mediators based 2nd generation Biosensors became unpopular.
GDH - NAD combination was however unaffected. There were however tragically more
than 100 deaths reported between 1992 and 2009 related to faulty glucose monitoring due to
various causes (Newman 2010).
6.6.3 Electrode Interference
Most glucose biosensors incorporate bio electrodes. Usually there are 2 or 3 types of
electrodes employed, namely working electrode, reference electrode and counter electrode.
Unfortunately all ox disable substance or species can get oxidised at the electrode without
selection including glucose but also substances like vitamin C (Ascorbic Acid),
Paracetamol(Acetaminophen) or uric acid which are also commonly present in blood apart
from glucose and thus may interfere with estimation of glucose concentration(Piechotta et.al
2005). Many efforts have gone into removing these interferences by coating of electrodes
with polymer membrane or mediators or some pre oxidising membranes meant for
interferents to make them non electro active. But nothing has worked satisfactorily. On the
contrary the membranes suppressed glucose signals and affected measurement. Attempts
therefore were made to use ISF (interstitial fluid) with a view that concentration being low,
there may not be appreciable interference. Other electrophoretic separation methods also
have been tried but the matters have got more complicated, more error from and also more
expensive. The research is continuing (Wang 2002).

56
6.6.4 Fouling
As stated above this was the serious problem to overcome. In vivo applications in particular
caused this problem of fouling of electrodes by various species such as whole cells and
proteins. New materials which would mimic the properties were developed to improve the
function. The modifications of polymers used in biosensors though a good way to get over
the problem, has not been satisfactory yet lining of electrodes with electro polymerised
conducting polymers has held some promise in overcoming this problem. Finally attempts
have also been made with use of anticoagulants notably heparin onto surfaces but this has
been ineffective and caused leaching into sample solutions (Zhang et.al 2000).
It would be appropriate at this stage to discuss the various ways currently being used to
monitor glucose in the body followed by more detailed discussion of enzymes as it is my aim
and objective to develop a device to measure blood glucose using enzymatic application in
this sensor, before we proceed to the next chapter of materials and methods.
There are 3 ways correctly being undertaken in Glucose measurement.
6.7.1 Measurement by finger pricking (Point of Care)
This is the single one off measurement of blood glucose by minimally invasive but painful
traditional method of checking the blood sugar at any given time in order to adjust the dosage
of medication (Insulin in particular). This is generally effective if done regularly in
conjunction with regular check-up of HbA1c to see the glycaemic control in previous three
months and suffices if the diabetic control is really good. However it does not give idea
about ups and downs in blood on continuous basis in order to avert the problems of hyper or
hypoglycaemic fluctuations over 24 hours and been painful every time to take the prick to a
diabetic.
All attempts have been made to split only the superficial layers of epidermal layers of skin
and to collect only interstitial fluid (ISF) for measurement to avoid pain but, are not
successful and not reliable either till to date.
6.7.2 Continuous Measurement of Glucose:
In the last 15 years especially in last 10 years attempts have been made putting in
considerable efforts and money to develop a minimally invasive subcutaneous insertion of
biosensor to get continuous monitoring of glucose levels in ISF which almost represents
matching blood glucose levels.

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