COMPARATIVE STUDY AND ANALYSIS OF NON-

ENZYMATIC GLUCOSE (NEG) SENSORS AND MODELLING

AND SIMULATION OF A HIGH PERFORMANCE NEG
SENSOR USING FINITE ELEMENT ANALYSIS

ADVANCED RESEARCH METHODOLOGY ASSIGNMENT

Submitted By,

AHANA FATIMA ALEX

Research Scholar
Reg. No. 1000800549

DEPARTMENT OF ELECTRICAL AND ELECTRONICS ENGINEERING

Manipal Academy of Higher Education, Dubai, UAE
(A constituent unit of Manipal Academy of Higher Education)

October 16, 2020

 ABSTRACT

Diabetes, the most critical health issue faced by today’s world is pulling down the entire
mankind into such a threat that the only solution to this incurable disease is continuous glucose
monitoring by both the diabetic patients and individuals who are at risk of getting it. The usual
and cost effective way of monitoring- the “prick test” cannot be done several times a day for a
long period due to its complexity or uneasiness. Therefore the most reliable solution is the use of
biosensors which detects the level of glucose from interstitial fluids, sweat, saliva or tear.
Glucose sensors can be broadly classified as invasive and non-invasive in which the latter is of
great dominance due to its accuracy and responsivity.
Therefore, this study aims at the design of a non-invasive glucose sensor. A high performance
non-enzymatic glucose sensor is designed and simulated. The function of high performance
sensor is simulated to observe its sensitivity in detecting the glucose level in blood. In this study,
a NEG sensor having a non-organic electrode namely ferrocynaide is modelled using Finite
element method.
The glucose concentration is measured by calculating the current generated when electrode
reaction occurs in the strip. Sensitivity is observed for different glucose concentrations. The
sensor detected glucose concentrations at values as small as 0.1mmol/L by generating a
corresponding current of 0.5 A/m2.
Therefore, this design was further compared with experimental results obtained from literature,
taken from standard international journals. Results show that among the various electrode
materials which are currently of great research interest, ferrocynaide shows promising outcomes
both in sensitivity and selectivity terms.
 LIST OF CONTENTS
Page

Title Page i
Abstract ii
List of Contents iii
List of Figures iv
List of Tables v
Abbreviation vi
Chapter 1: Introduction to the proposed work 01-06

Chapter 2: Literature Review 07-10

Chapter 3: Research Gaps 11

Chapter 4: Problem Statement 12

Chapter 5: Research Questions 13

Chapter 6: Objectives 14

Chapter 7: Rationale of Research 15

Chapter 8: Research Methodology 16-19

8.1. Research Methodology – Flow Chart 16

8.2. Modelling and Simulation 17

8.3. Finite Element Analysis – COMSOL Multiphysics 17

8.4. Design Basics 18

8.5. Comparative study and analysis 19

Chapter 9: Data Collection 20- 25

Chapter 10: Design and Simulation of NEG Sensor using Finite Element 26- 28

Analysis
Chapter 11: Results & Inferences 29- 31

Chapter 12: Implications & Conclusion 32

References 33- 35

List of Figures
Figure 1.1: Types of glucose sensors and electrochemically active materials in it. 03
 Figure.2. Evolution of glucose monitoring system from invasive to
Figure 1.2: 04
non-invasive
Figure 1.3: The working principle of enzymatic glucose sensor 05
Figure 9.1: Lab On-chip system for blood sugar monitoring 20
Figure 9.2: Output graph of CuO sensor 21
Figure 9.3: Output graph of PET electrochemical sensor 22
Figure 9.4: Output graph of SPCEs sensor 24
Figure 9.5: Output graph of NEG sensor using bioelectronics pH control 24
Output graph of NEG sensor using polysynthetic and ferricyanaide thin
Figure 9.6: 25
film
Figure 10.1: 2D domain model representation of unit cell 26
Figure 10.2: Mesh Generated 27
Figure 10.3: Extremely fine mesh near the sensing region 28
Concentration Profiles of ferricyanide ion at 50μmol/L glucose
Figure 11.1: 29
concentration
Concentration Profiles of ferricyanide ion at 500μmol/L glucose
Figure 11.2: 30
concentration
Concentration Profiles of ferricyanide ion at 1000μmol/L glucose
Figure 11.3: 30
concentration
Figure 11.4: Output Plot 31

List of Tables
0
Table 1.1: Blood glucose values specified by NICE
2
1
Table 8.1: List of input parameters
7
2
Table 9.1: CuO based NEG sensors and their sensing characteristics
1
 2
Table 9.2: Sensing ability of electrochemical sensor for different samples
3
Sensing ability of ferricyanide and negatively charged GOx entrapped 2
Table 9.3:
SPCEs
3

List of Abbreviations
CGM Continuous glucose monitoring
CuO Copper oxide
CV Cyclic Voltammetry
DM Diabetes Mellitus
GDH Glucose dehydrogenase
GOx Glucose oxidase
ISF Interstitial Fluids
NEG Non-enzymatic glucose
NICE National Institute for Clinical Excellence
WHO World Health Organization
 CHAPTER 1
INTRODUCTION TO PROPOSED RESEARCH

Diabetes mellitus (DM) generally called as diabetes, are a class of metabolic disorders indicated
by a rise in blood sugar or blood glucose level in the body for an extended period of time. It is
condition that reduces or in the worst case, stops the ability of human body, to process blood
sugar, retention of which leads to critical health issues. There are different types of diabetes such
as:
 Type 1 diabetes or juvenile diabetes which as the name indicates is commonly found in
children.
 Type 2 diabetes- the most common type, usually found in adults.
 Gestational diabetes which is seen in some pregnant women with no previous records of
diabetes.

According to statistical studies done by the global diabetes community of UK in the 2018, India
is a home for over 30 million (diagnosed) diabetes patients making it the second largest country
with people suffering from diabetes after china [1]. Juvenile diabetic records are also in the lead.
Adding more to this, the international diabetic federation says that 1 in every 10 people is living
with diabetes and around 463 million people of the world population are diabetic patients [2].
According to their diabetes atlas published in the year 2015, the diabetic patients in India were
around 62.9 million and are expected to jump up to 123.5 million by 2040. World health
organization (WHO) also gives the same statistical account for diabetic patients worldwide.
With the modernization and sophistication of lifestyle, getting all that we need at our doorsteps
became its new notion leading us to a more sedentary life pattern – which could be claimed as
the major culprit that leads to this disease. However, sedentary lifestyles, being overweight or
family history of diabetes are not the only reason for getting affected. Many a health issues and
diet and nutritional vulnerabilities pave the path for diabetes for people living in urban as well as
rural areas at the same rate.
The greatest consequence of diabetes is that it is incurable and over a period of time, high blood
glucose leads to critical problems such as cardiovascular diseases, kidney diseases, stroke, foot
problems, eye problems, nerve damage, dental diseases to list a few. But thanks to the

1
technological advancements and great innovations in health care, many a diagnosing and
monitoring systems are available in surplus however the feasibility of making use of these
devices by all class of people (whether rich or poor) is still a point of question.
Apart from taking proper medication including insulin injections, a major step that should be
taken by any diabetic patient is monitoring the glucose level on a regular basis. Careful and
continuous monitoring of blood glucose level is the only solution to make sure that the blood
glucose levels are within the target range specified by the doctors for both diabetes patients and
people who are more prone to get diabetes. Continuous glucose monitoring (CGM) is
recommended for diabetic patients by all health professionals. Typically, a diabetes patient
should monitor his/her blood glucose level (2-20mM range) for up to five times per day so as to
regulate the metabolic rate. The National Institute for Clinical Excellence (NICE) has provided
the guidelines on range of targeted blood glucose levels and is as shown in table. 1[1]. Adding to
it, the target range of non-diabetic people are also listed out in the table as stated by the
International Diabetes Federation [3, 4, 5]. Even so, the target range of diabetic patients is
always set by the diabetic consultant.

Table.1.1. Blood glucose values specified by NICE

“Prick test” which involves extraction of blood is the most commonly followed technique that is
most precise and affordable. But drawing blood each time a day by pricking is a tedious and
painful process especially for children with type 1 diabetes. Not only people with diabetes should
monitor the blood glucose level but people having family history of diabetes should closely

2
monitor their blood sugar level. People suffering from kidney issues, polycystic diseases and
pancreatic problems should also have a regular check on their glucose levels. Due to the
discomfort and uneasiness created by the “prick test”, it is never done more than once in a day by
majority of the patients which again leads to health repercussions which is an unknown fact to
common man.
CGM has now become an easy task with the innovations brought forth in glucose sensors. It is
now as easy as it is, as glucose values could be found using these sensors from body fluids such
as interstitial fluids (ISF), tears, saliva and sweat. Also, there are long term implantable glucose
sensors, which could be implanted in the body safely for a year or more. Therefore, these
currently available glucose sensors can be broadly classified into two main types- enzymatic and
non-enzymatic [6] as shown in figure 1.

Figure.1.1 Types of glucose sensors and electrochemically active materials in it.

Enzyme based glucose sensors which are widely in use now, are modelled using glucose

3
dehydrogenase (GDH) or glucose oxidase (GOx) which reacts with glucose molecules producing
electrical responses which is correlated to concentration of glucose [7]. Non-enzymatic glucose
(NEG) sensors on the other hand directly oxidize the glucose molecule on the surface of the
sensor where the atoms present there at the surface acts as electrocatalysts. Different types of
enzyme based glucose sensors could be seen in figure 2 [8].

Figure.1.2. Evolution of glucose monitoring system from invasive to non-invasive

Enzymatic sensors being the most commonly used are always of research interest so as to
improvise the design to the better. Majority of these glucose sensors or glucose meters are
classified as amperometric sensors. In these sensors, the reducing property of glucose is
measured as a current [9]. Here glucose reacts with glucose oxidase GOx and a mediator. In this
case, the mediator is oxygen thus forming the glucose oxidase enzyme GOx(ox) . The reduced
enzyme GOx(red) then reduces two mediators M ox ions to M(red) which is then
converted (oxidized) back to Mox at the surface of the electrode. Current thus
generated by this reaction is measured using the electrodes of the sensor. The basic reaction
equations that take place within the enzymatic sensors are as below [9].
Glucose +O 2 GO x Gluconic acid + H O …………..…1
2 2
⇒

Glucose +GOx(ox) → Gluconic acid + GOx(¿) ……………..2

GOx(¿) +2 M (ox) → GOx(ox ) + 2 M (¿) +2 H +¿¿ ...…………...3

4
 2 M (¿) → 2 M (ox) + 2 e−¿¿ ……………..4

The oxidation process described by equation 4 is measured as the current by the sensor
electrodes at its surface. Conductivity, resistance, diffusion and rate of reaction by Michaelis-
Menten rate law are few of the important physics involved in the working of glucose sensors.
The complete process of enzymatic glucose monitoring is illustrated in figure 3 [8].

Figure.1.3.The working principle of enzymatic glucose sensor (described by the basic equations)

However, in this type of sensors the oxidation process of glucose does not happen at the sensor
electrodes which evaluate the current. Instead, the reaction first oxidizes and then reduces the
enzyme thus making the sensor independent of concentration of any other oxidizable specimen
in the sample fluid and dependent on only the glucose concentration. Moreover, oxygen present
around in the sample environment being considered as the oxidant, suffers from decelerated
kinetics. Also, the oxygen concentration that reacts with the sample fluid from the atmosphere
unsettles the rate of oxidation. Hence there will be discrepancy in the blood glucose value thus
monitored. The variation being very small from the actual value does not affect the diabetic
patients within the normal ranges, border ranges and slightly higher than the target ranges but
affects the patients with very high blood sugar levels and patients with other critical health

5
conditions such as kidney failure and heart diseases as these health conditions and diabetes
complement each other or trigger the situation to worse.
Therefore, need of a better performance glucose monitoring sensor that gives accurate values of
glucose levels in the body is inevitable. NEG sensors gain its importance at this scenario as it
claims to be more advanced than enzymatic sensors and are more reliable. In NEG sensors,
oxygen is replaced by inorganic oxidants thus accelerating the electrode kinetics. Many studies
and researches focuses on this sensor designs depending on different materials used as electrodes
and different oxidizing agents and many are in the process of clinical trials as there is still room
for improvement with the existing models. This study therefore focuses on design and simulation
of a novel non-enzymatic amperometric glucose sensor which would cover up the flaws of
existing sensors and yield better results than the conventional ones.

6
 CHAPTER 2
LITERATURE REVIEW

Heba Abunahla, et al. [7] the work focused on the design of a novel Pt/CuO/Pt metal-oxide-
metal (MOM) glucose sensor. Photolithography was the technique used for the fabrication which
helps in R & D cost-cutting. The sensor thus modelled claims to have a sensing range of 2.2-
10mM of glucose concentration which is the complete target range. The ability of this sensor to
sense glucose at neutral pH conditions make it unique from other glucose sensors. However the
paper aims at more buffer tests before actually considering the real time fabrication as buffer
tests provide arbitrary results.
Yusengh Wang, et al. [10] proposed a sensor design using thin film polyethylene terephthalate
(PTE) as gold electrodes. The work states that compared to other wearable sensors, this sensor
will be less expensive, simple to use and minimal instruments would be incorporated. It shows a
large span of time stability which is duration of 4 weeks. The glucose range could be analyzed
from sweat. Yet the sensing range of glucose sensor thus proposed does not meet the target
range.
Ming-Jie Lin, Ching-Chou Wu and Ko-Shing Chang [11] the inorganic oxidant used in this
paper were ferricynaide. Normal strip tests uses screen printed carbon electrodes (SPCEs) the
same was applied in the study. The sensing limits were in good agreement with the target values.
GOx were also included in the study and its sensing effects were identified.
Kun Tian, Karthikeyan Baskaran and Ashuthosh Tiwari [12] non-enzymatic sensors were
designed using three different metal oxides namely, copper oxide (CuO), cobalt oxide and nickel
oxide. All the three metal oxides showed good sensing capacity (2-20mM range) even so, all of
them showed variations in their performance due to difference in conductivity property and
different electrochemical activities. Among these three oxides, copper oxide showed better
sensitivity and permeability for glucose detection.
Anchu Ashok, Anand Kumar and Faris Tarlochan [13] the paper also focused in the use of
CuO nanoparticles as oxide. The oxides were synthesized using three different modes. Out of the
3 modes, the nanoparticles obtained using Cu-colloid showed best results with minimum time
response. Also its stability was commendable. However steady state current effects are to be
studied more.

7
Won-Chul Lee, et al. [14] the conventional enzymatic and non-enzymatic sensors were studied
and a hierarchical bimetal namely aluminum-nickel allow was employed in both type of sensors.
Direct and catalytic oxidations of enzymatic and non-enzymatic sensors were observed and the
sensing sensitivity was monitored. However reliability of this work is better than the finger
pricked test methods but not as capable as other techniques using ferricynaide.
Xenofon Strakosas, et al. [15] bioelectronics pH control lays the base for this work. NEG
sensors are being used in this study. The normal detection target range of 2mM-20mM is
achieved by this method. A reversible and localized pH change induced electronically aided in
the sensing process. The study focused on sensing glucose values from neutral pH samples such
as sweat and tears.
Dae-Woong Hwang, Saram Lee, Minjee Seo and Taek Dong Chung [16] this paper aims at a
review on latest advancements in electrochemical NEG sensors. Sensors using different materials
such as platinum, gold, metal alloys, metal oxides and other organic materials were considered in
the study. Significance and performance of each sensor and/or categories of sensors were studied
and listed. Importance of commercializing these sensors beyond laboratory testing was discussed
in the paper. Out of the many oxidizing materials taken, ferricynaide seems more promising.
Jyun-Sian Ye, Chin-Wei Chen and Chien-Lian Lee [17] designed NEG sensors using Pd
nanocubes. They are stable catalyst for glucose sensors. The nanocubes (6.3 x 10^-5 Ccm^-2)
shows better performance of about 1.45 times than nanoparticles (4.3 x10^-5 Ccm^-2). These
nanocubes have greater oxidation capabilities and have greater sensitivity. The paper demands
more study and investigation on nanocubes.
Mark P. Christiansen, et al. [18] the study assessed the preciseness and performance of a 4th
generation glucose monitor. Clinical trials were conducted with 88 subjects. The data and
analyzed results could be used for validation purposes in our study.
Nur Alya Batrisya, et al. [19] nanomaterial based transducers were studied in this work for
developing glucose sensors. The effect of composite on the electrodes/ transduction was keenly
studied in the work and conclusions were drawn that these composites could further help in the
electrode modification and improvement. However, the study states that it should be further
extended for optimization of transduction.
Xiao Wang, Chuang-ye Ge, Ke Chen and Yu Xin Zhang [20] this work has many a similarity
with literature [12, 13]. Here too, three types of CuO nanostructures were acquired by kinetic

8
control. As in [13], rough petal like structured CuO showed quantitative sensitivity. The work
managed in designing an ultrasensitive and immensely stabilized NEG sensor. Applicability in
real time is yet to be investigated.
Yan Zhong, et al. [21] CuO nanostructure based ultrasensitive NEG sensor is designed in this
work. Nanostructures were grown in an in-situ growth method on carbon clothes. Cyclic
voltammetry (CV) and chronoamperometry were the techniques used to detect the sensitivity and
performance of these non-enzymatic electrochemical glucose sensors. Applied potential used
was 0.55V.
Marie Sherman [22] this work, describes the complete working principle of glucose sensors and
the physics involved it. Rather than design of a novel sensor, the work focused on design of a
simple sensor for detailed understanding on the same. The work greatly helps a researcher in his
way to design of enzymatic or non-enzymatic glucose sensors.
Li Hua, Chun-Yan Guo and Cai-Ling Xu [23] bimetallic superstructures such as Cu-Ag were
used in the study for the design and modelling of ultrasensitive non-enzymatic glucose monitors.
The sensor design showed extreme sensitivity ranges covering the target range and more. Sudden
dip or rise in blood sugar could be identified few minutes before the visible reaction outcome
occurs. Therefore precautionary actions can be initiated which otherwise leads to critical
complications.
Fatma Arslan and Umut Beskan [24] potassium ferricynaide film is used here along with two
other polymers in the design of glucose sensor which is non-enzymatic and non-invasive. The
amperometric sensor immobilizes the glucose oxidase on the polymer-ferricynaide
combinational electrode surface. However temperature conditions effect the performance of this
sensor.
N. S. Oliver, C. Toumazou, A. E. G. Cass and D. G. Johnston [25] this paper too, is a study
and review on existing sensors, their sensitivity, performance and reliability like [22]. Different
models and materials are reviewed and practicality of each material was cross checked.
Technologies that are under development of glucose sensors and engineering role in modelling
were pointed out. Glucose sensor error grids were also mentioned clearly.
Frans C. Schuit, Peter Huypens, Harry Heimberg and Daniel G. Pipeleers [26] this work
states the importance of glucose monitoring in other glucose related cells in the body such as
pancreases, gut and hypothalamus. The importance of glucose monitoring in pancreatic β- cells

9
and disadvantages if not monitored were discussed. Need for a sensor design to sense the blood
glucose value in pancreatic β- cells was thus proposed.

Literature review was done on both quantitative and qualitative studies. Literature works [22]
and [25] are qualitative study and [12, 14 and 19] are quantitative as well as qualitative in nature
while the rest of the papers were on quantitative study.

10
 CHAPTER 3
RESEARCH GAP

1. An optimal non-enzymatic amperometric glucose sensor design that is ultrasensitive and

yields result instantly and at the same time are non-reactive to the organic or inorganic
oxidase is not yet developed. Many researches and studies are focused on the same.
2. All the current glucose sensors fail to meet the tradeoff of selectivity and sensitivity i.e. many
sensors which are designed with ultra-sensitivity capabilities however selectively reacts with
the oxides which is not a desired property and vice-versa.
3. Out of the n number of materials that could be used for the electrode designs CuO and
Ferricynaide shows better performance both sensitivity wise and selectivity wise. Adding
more to that, these materials consume minimal time in generating results. Therefore these
material study and designs using them could help in overcoming the drawbacks of existing
techniques.

11
 CHAPTER 4
PROBLEM STATEMENT

1. According to global health organizations, diabetes has the potentiality of hitting the planet as
one of the largest deadliest disease by the year 2030. India has largest number of diabetic
patients after china and it is observed that in India, the growth rate in diabetic patients for the
last 15 years is 100%. To fight against diabetes by people who are more vulnerable to this
disease and to control the glucose levels within the target range by diabetes patients the first
and foremost step should be continuous glucose monitoring (CGM).
2. CGM using “prick tests” are not practical possible hence the use of non-invasive methods
such as use of enzymatic and non-enzymatic glucose (NEG) sensors became more prominent
of which NEG sensors are more over powering because of its better performance and
functionality than enzymatic sensors. However, selection of electrode material is a crucial
point in designing.
3. In NEG sensors, the concentration of glucose in a specimen is measured using an
amperometry which is the measure of electric current. An applied voltage leads to oxidation
of glucose and the current thus generated as a result is measured at the electrode. In a good
glucose sensor design, the glucose concentration and the current will always follow a linear
relationship. Yet in many designs this linearity is lacking.
4. Oxygen when used as oxidant reacts with the electrode in an uncontrolled fashion thereby
decelerating the kinetic reaction. If oxygen is replaced by inorganic oxidants, kinetic reaction
will be enhanced.

12
 CHAPTER 5
RESEARCH QUESTIONS

1. What are the effective non-enzymatic amperometric glucose sensor designs that have high
stability, ultra-sensitivity, selectivity and time managed?
2. What are the different techniques used in design of NEG sensors with different electrode
materials and what are the advantages of each of these methods?
3. How to analyze and design a NEG sensor that can overcome any of the existing drawbacks?

13
 CHAPTER 6
OBJECTIVES

1. To study and compare the different design methods of NEG sensors that is of research
interest and to understand the advantages of these methods.
2. To study the characteristics of inorganic oxidant – ferricynaide- which has gained so much of
research attention.
3. To design and simulate a NEG sensor using the best results obtained by comparative study
and to modify the design by varying parameters so as to eliminate at least one drawback of
existing sensors.

14
 CHAPTER 7
RATIONALE OF RESEARCH

1. The primary need for this research is that, according to leading health care organizations such
as Centers for disease control and prevention and World health organization, diabetes is rated
as one of the top ten (seven) fatal diseases that will hit the planet at a severe range of one in
every five people within a decade. This lifestyle disease though incurable, could be
controlled and well maintained within the target range if closely monitored regularly.
Therefore, a good monitoring system is an inevitable need.
2. The most efficient method of monitoring glucose level is with the use of glucose sensor.
Most of the sensors available today use a wide range of sensing electrodes and its
performance vary from material to material. However, studies and researches indicate that
use of organic electrodes alters the results and therefore use of NEG sensors could provide
accurate results. Therefore, effectiveness of NEG sensors over enzymatic sensors should be
examined widely. Hence the research will focus on the design of a NEG sensor.
3. Studies shows that materials such as CuO and Ferricynaide gives instant results with
maximum sensitivity and selectivity – which is a major research gap found in other
conventional techniques. More studies and researches are deployed in this area of material
selection. Therefore, these electrode materials will be used in the sensor design.

15
 CHAPTER 8
RESEARCH METHODOLOGY

The research focuses on modelling and simulation of a NEG sensor using ferricyanide as
electrode and observes its performance parameters. Thus obtained parameters will be compared
with experimental results of other NEG sensors prevailed from literature review so as to draw
conclusions on the effectiveness of the sensor thus modelled.

8.1 Research Methodology – Flowchart

Design and Simulation of a NEG glucose Sensor

2D single strip Ferricyanide -electrode

interdigitated electrode material

Finite Element Analysis –

COMSOL Multiphysics

Current density
Electrochemistry and concentration
– Module used of glucose –
compared

Final Results compared with

experimental results in literature

16
8.2 Modelling and Simulation

A non-enzymatic glucose sensor will be designed and simulated. An inorganic oxidant namely
ferricyanide which has very speedy electrode kinetics will be used as the electrode. The
advantage of such oxidant is that the determined current will be made independent of the
concentration of oxygen and there is no limitation of slow process or kinetics. A simple 2D
model will be the prior focus with a single strip having a 100 μm width. A constant electrolyte
potential will be considered assuming electric field to be negligible due to the very low
resistivity. Steady state analysis is considered in this study. The list of input parameters taken for
the study is as shown in table 8.1.

Table 8.1 List of input parameters considered in the simulation study

Parameters Unit
External glucose concentration umol/L
Ferrocyanide concentration umol/L
Ferricyanide concentration mmol/L
Maximum rate of reaction mol/L/s
Michaelis-Menten constant mmol/L

8.3 Finite Element Analysis - COMSOL Multiphysics

Finite element analysis COMSOL Multiphysics is used here for the design and simulation of a
NEG sensor. COMSOL Multiphysics as the name suggests is software that could incorporate
different physics or phenomenon into a single design process. The different modules in the
software have much built-in functionality that aids in easy designing.
The electroanalysis interface that comes under the electrochemistry module is used in our
modelling. Stationary study is used and steady state condition is assumed. Necessary geometric
parameters will be created and material properties will be specified. All the required boundary
conditions and physics will be defined to simulate the output. Since diffusion of chemical species
takes place across the electrode, Fick’s law of electroanalysis interface is used to define the

17
process of diffusion.

8.4 Design Basics

Researches says that, in the design of any medical devices, the engineering support stands as the
backbone as it helps in developing a model that could predict the outcome and the relationship
between each parameters considered which if done experimentally would have become very
expensive. Adding more to it, these experimental trials are limited by the uncertainty to identify
the effect of each input parameters on the output and how the output could be improved.
Therefore, mathematical modelling and simulations are very essential. The very basic design
equations that helps in building the framework of the model is stated below.

The constant electrolyte potential assumed to be 0 as shown below in equation (1) [31], [32].

Φl = 0 ………..… 1

At steady state condition, diffusion equation defined by Fick’s law of the interface taken can be
reduced to 0 as shown by equation (2) [31], [32].

∇ . ( D i ∇ ci ) =0 ………..… 2

Where Di is the Diffusion Co-efficient (m^2/s) of each species i. and Ci is the Concentration of glucose
(mol/m^3).

Above the electrode, reaction takes place at the solution phase between the glucose and the ferri-
anion which is as shown in equation (3) [31], [32].

………..… 3
Glucose + ferri products + ferro

The rate of the reaction is given by Michaelis-Menten rate law as in equation (4) [31], [32] where
Vmax is the maximum rate of the enzyme – catalyzed reaction, c glucose, the concentration of glucose
and Km is Michaelis-Menten co-efficient.

………..… 4

18
 c glucose V max
R=
(1+ K m c glucose )

The current density could be found using equation (5) [31], [32] which is as shown below

( n−α c ) F η (−α c ) F η …..…5

(
i loc=nFk 0 c ferro exp ( RT )
−c ferri exp ( RT ))
Where iloc is the electrode current density in A/m2, n is the number of electrons involved in the
electrode reaction, ko is the heterogeneous rate constant of the reaction, η is the over-potential at
electrode, αc is the cathodic charge transfer co-efficient, F the Faraday constant and R is the
universal gas constant.

8.5 Comparative study and analysis

Current value and glucose concentration of different NEG sensors will be observed to evaluate
its performance parameters. Experimental results of latest studies found in various literatures
taken from international standard journals such as IEEE, Springer and Elsevier are used for this
purpose.

CHAPTER 9

19
 DATA COLLECTION

The results obtained from the proposed model and simulation will be compared with the readily
available experimental results of literature review. Few output data from literature are as below.

From [7], the lab on chip system for measure the blood sugar value is modelled as in figure. 9
Sensing ability of the sensor thus modelled was checked for glucose concentrations 3.9mM,
5.6mM and 7.8mM respectively.

Fig.9.1 Lab on chip system for blood sugar monitoring [7]

A 1V dc voltage was applied across the sensor, which is the minimum voltage requirement for
the working of the sensor. The consequential current is measured and the electrical stability of
the device is also recorded in the absence of glucose. In the next step, the current will be
recorded in the presence of glucose [7]. The output of the sensor showing the current data with
respect to concentration of glucose in blood is as in figure 9.2 [7]. From the graph obtained,
current values could be equated to respected equations to analyze the response time and device
saturation. In this model, device saturation occurs at a glucose concentration of 10.0mM
(180mg/dl). This output graph could be used for comparing the results of proposed model.

20
 Figure.9.2 output graph of CuO sensor [7]

Few latest NEG sensors and their detection limits and sensitivity are shown below in a tabular
format as in table 9.1 [7]. These reference values are all experimentally tested.

Table 9.1 CuO based NEG sensors and their sensing Characteristics [7]

Electrocatalyst Linear Detection Sensitivity pH

Range Limit (μA mM-1
(mM) (mM) cm-2)
CuO nanosheets 0.5–10 1 x 10-4 520 13
CuO nanospheres 0-2.56 1 x 10-3 405 13
CuO nanoflowers 0-5 1.71 x 10- 2657 13
3

Carnation-like CuO 0-5.5 98 x 10-6 3150 13.2

Hierarchical Nanostructures
Flower-like CuO 4.5 x 10-2 - 6.87 x 10- 1710 13
hierarchical nanostructures 1.3 x 10-1 3

CuO nanorods 0-5 220 x 10-6 1834 14

Sandwich-structured CuO 0-3.2 1 x 10-3 5343 13
Cu/Cu2O/CuO ternary 0-0.1 0.39 x 10- 8726 13
3
composite hollow spheres
CeO2@CuO core shell 1-8.9 0.019 x 3319 13
nanostructure 10-3
Nanocomposites of CuO 5x 10-5 – 50 x 10-6 1610 13

21
 and single-wall carbon 1.8
nanotubes
CuO nanoparticles 0.21 x 10-3 0.21 x 10- 700 13
3
–12
Pt/CuO/Pt metal-oxide- 2.2 – 10 1.42 2921 7
metal

From reference [10], we see that, a thin film of poly ethylene terephthalate (PET) is used as the
sensing material for glucose sensor for detecting the blood sugar level from sweat. The output
characteristics and sensing ability are as shown in figure 9.3 and Table 9.2.

Figure.9.3 output graph of PET electrochemical sensor [10]

Table.9.2 sensing ability of electrochemical sensor for different samples [10]

22
From reference [11] a combination of oxidase including ferricyanide entrapped on screen
printed carbon electrodes (SPCEs) can be seen as glucose sensing elements. The different
sensing electrodes and its combinations and their corresponding sensitivity and limit of detection
(LOD) are shown in table 9.3.

Table 9.3 sensing ability of ferricyanide and negatively charged GOx entrapped screen printed
carbon electrodes [11].

The different glucose concentrations and their corresponding current data – the output of the
sensing device is shown in figure 9.4 [11].

23
 Figure.9.4 output graph of SPECs sensor

In reference [15], a NEG metal oxide glucose sensor that functions in neutral fluids is modelled.
Here too, sweat is considered as the analyte. The output graph is as shown in figure 9.5.

Figure.9.5. output graph of NEG sensor using bioelectronics pH control.

24
From reference [24], we see that polysynthetic materials such as polyaniline and
polyvinylsulfonate are combined with potassium ferricyanide to form the sensing electrode. The
result of such a novel study is as in figure 9.6.

Figure.9.6. output of NEG sensor using polysynthetic and ferricyanide thin film

25
 CHAPTER 10
DESIGN AND SIMULATION OF NEG SENSOR USING FINITE
ELEMENT ANALYSIS

The study aimed at the modeling and simulation of a 2D sensor strip that could sense the glucose
concentration and provide corresponding electric signals in the form of current. The 2D domain
represents a 100μm wide unit cell of solution above an inter-digitated electrode. The actual
geometry in real time is a replica of this unit cell in the x- coordinate (axis). The 2D assumption
is made so that the cell could be extended as much as required in the taken direction. At the
center of the cell, within the range of 37.5μm ˂ x ˂ 62.5μm lays the anode. It is at the center of
unit cell most of the reaction occurs in the anode.

Figure.10.1. 2D domain model representation of unit cell

Electroanalysis interface of electrochemical module is used for simulation. Stationary study is

done as this analysis evaluates the steady state current output obtained for constant given
voltage. Current and concentration profiles for different values of glucose concentrations are
compared and analyzed using parametric sweep. Stoichiometric coefficients of ferro and ferri
cyanides are given as 1 and -1 respectively. The glucose range was given from 50μm– 1000μm.
Suitable boundary conditions were applied. Reaction rate of glucose and average current density
are calculated. Extremely fine meshing was done to get a very good result including sensitivity

26
and sensibility rate. Maximum element size was also defined rather than giving predefined
values.

Figure.10.2 Mesh generated

27
Figure.10.3. Extremely fine mesh near the sensing region

28
 CHAPTER 11
RESULTS & INFERENCES

Figures 11.1, 11.2 & 11.3 shows typical concentration profiles for the ferrocyanide ion in unit
cell for different glucose concentrations. Ferrocyanide is obtained in the solution as a result of
glucose oxidation. It reacts at the anode at the middle of the strip thus providing a cathode-
current from which glucose concentration could be obtained as shown in the surface
concentration plot. The process that takes place within the sensor by oxidation and reduction is
“redox cycling”. This cycling phenomenon thus provides an amplified current which has a linear
relationship with the concentration of glucose. The plot is as shown in figure 11.4.

Figure.11.1 Concentration profile of ferricyanide ion at 50μmol/L glucose concentration

29
Figure.11.2 Concentration profile of ferricyanide ion at 500μmol/L glucose concentration

Figure.11.3 Concentration profile of ferricyanide ion at 1000μmol/L glucose concentration

30
Figure.11.4 Output Plot - Current density corresponding to concentration of glucose

CHAPTER 12

31
 IMPLICATIONS & CONCLUSIONS

A comparative study on the sensing property of different NEG sensors including CuO and
Ferricyanide were done using experimental data from literature survey. All literature papers
taken for this study was therefore from international standard journals. From this comparison,
it was found that sensors with inorganic oxidant ferricyanide provided promising results than
other currently used ones.
Design and simulation of a NEG sensor with non-oxidant electrode ferricyanide was
therefore done and found that they yielded better performance both sensitivity wise and
selectivity wise. The glucose sensitivity and corresponding electric current produced by the
electrode on sensing the glucose were found. The results shows that for glucose values as
small as 0.1mmol/L (0.0001M) a corresponding current is generated ⁓ 0.5A/m 2 showing the
sensitivity of the sensor which is the most desired property of any sensor.
The sensor thus designed with a non-enzymatic electrode could sense the glucose levels of a
diabetic patient without the regular “prick-tests” and could be used frequently – the only way
to control this incurable life-style disease, from body fluids such as sweat, saliva or tear
much more accurately.
Considering the substrate’s excellent pliability, the NEG sensor is expected to be further
fabricated into devices that could sense glucose from sweat on a real-time base and could be
worn easily like a sticker or a plaster.

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32
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