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A non-invasive microcontroller based

estimation of blood glucose concentration


by using a modified capacitive sensor at
low frequency
Cite as: AIP Advances 9, 105027 (2019); https://doi.org/10.1063/1.5116059
Submitted: 21 June 2019 • Accepted: 01 October 2019 • Published Online: 23 October 2019

Abhinaba Dutta, Satish Chandra Bera and Kamalesh Das

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Paper published as part of the special topic on Biophysics and Bioengineering

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AIP Advances 9, 105027 (2019); https://doi.org/10.1063/1.5116059 9, 105027

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A non-invasive microcontroller based estimation


of blood glucose concentration by using
a modified capacitive sensor at low frequency
Cite as: AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059
Submitted: 21 June 2019 • Accepted: 1 October 2019 •
Published Online: 23 October 2019

Abhinaba Dutta,1,a) Satish Chandra Bera,2,b) and Kamalesh Das3,c)

AFFILIATIONS
1
Department of Electrical Engineering, Academy of Technology, P.O.- Aedconagar, Adisaptagram, Hooghly 712121, India
2
Instrumentation Engineering Section, Department of Applied Physics, University of Calcutta, 92, A.P.C. Road,
Kolkata 700009, India and Techno Main, Salt Lake, Kolkata 700091, India
3
Murshidabad Zillah Parishad, Lalbagh, Golapbagh, Murshidabd 742149, India

a)
Tel.: +919748773297, Electronic addresses: abhinaba.dutta@aot.edu.in and abhinaba_100u@rediffmail.com
b)
Tel.: +919433156018, Email address: scbera_cal52@rediffmail.com
c)
Tel.: +8100773297

ABSTRACT
In the present work, a noninvasive technique of glucose concentration measurement in human blood has been developed. A semicylindrical
capacitive sensor is used to measure the blood glucose concentration in terms of capacitance of the sensor. It is shown that this capacitance
varies linearly with glucose concentration in human blood. A low frequency operational amplifier based circuit is designed to measure this
capacitance in terms of an output voltage signal. A linear relation between the ratio of this output signal to input supply with blood glucose
concentration is derived in the paper. A microcontroller based software program is designed to measure this ratio and to display glucose
concentration in a LCD display unit in digital form. The performance study of the proposed blood glucose concentration measurement
circuit with respect to standard glucometer and that of the proposed blood glucose concentration display unit are carried out in the present
work. The experimental results are reported in the paper in both tabular and graphical forms. The linear characteristic graphs and close
conformity of the results of the proposed technique with those of standard glucometer are observed. The measurement error with respect to
glucometer is found to be within ±3.5%.
© 2019 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license
(http://creativecommons.org/licenses/by/4.0/). https://doi.org/10.1063/1.5116059., s

I. INTRODUCTION device. The minimum invasive methods like micro dialysis probe
method, fluorescent sensor method, glucowatch method etc. are also
Measurement of glucose concentration in human blood is an painful methods. So painless non-invasive techniques with good
essential requirement for the medical treatment of any person by reliability and accuracy is the recent trends in blood glucose mon-
a physician. The existing measurement techniques may be of three itoring. These techniques may be of various types (Klonoff, 1997)
types (Gonzales et al., 2019) namely, invasive, minimally invasive such as near-infrared (NIR) light spectroscopy type, mid-infrared
and non-invasive. In the conventional biochemical invasive tech- (MIR) light spectroscopy type, far-infrared (FIR) spectroscopy type,
nique, a certain volume of blood is drawn from the human body Raman spectroscopy type, polarized light rotation type, impedance
to determine the glucose content in the blood sample through bio- spectroscopy type etc. In optical spectroscopy type, an optical beam
chemical analysis of the sample. This technique is very painful for a passing through a selected region of human body suffers from a
person. At present, a less painful minimally invasive portable glu- change in spectrum which is taken as a measure of glucose concen-
cometer technique is being used to measure blood glucose where tration and measurement accuracy is determined by calibrating the
only a drop of blood is used by pricking any finger with a pricking instrument with the help of an invasive type biochemical standard

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-1


© Author(s) 2019
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instrument or glucometer. In this analysis, the glucose present in by using a multi sensor technique (Boehm et al., 2010) where the
blood in organs like fingertip, finger web, cuticle, forearm, earlobe ultrasonic, electromagnetic and thermal techniques are combined
etc. changes the spectrum of light passing through the organ and for accurate estimation of blood glucose from the accuracies of dif-
from the spectroscopic analysis of this light, the glucose content of ferent sensors. In high frequency analysis (Liao et al., 2003; Gourzi
the blood is estimated. But these techniques are not yet standardized et al., 2005) of dielectric properties of blood glucose solution, it is
with acceptable accuracy and reliability. So various works are still observed that effective dielectric constant decreases linearly with
being reported to develop a reliable noninvasive glucose monitor- increase of glucose concentration. This is also similar to the results
ing technique. In an experimental work on bio-impedance analyser of low frequency analysis as stated earlier.
type blood glucose monitoring technique (Li et al., 2018), it is shown In the present work, a noninvasive low frequency capacitive
that the presence of glucose in blood changes the effective conduc- measurement technique of blood glucose concentration in human
tivity and permittivity as well as impedance of a living organ between blood has been studied. In this technique, a curved plate capacitor
two electrodes at low RF frequency in the range from 1kHz-1MHz. has been designed by fixing the plates on a silicon tube of suitable
In this work, it is also observed that at low frequency near 1kHz, length and diameter by means of thin layer of adhesive without any
the conductivity increases and the permittivity decreases almost lin- air gap. The dimensions of the silicon tube are so selected that any
early with increase of frequency, but at high frequency, they have one of middle finger, fore finger and ring finger of any arm may
little variation with frequency. In another experiment (Li et al., 2017) be inserted in the silicon tube without any air gap embracing the
on spiral microstrip resonator with blood mimicking phantom, it whole length of the tube. A mathematical model has been devel-
is observed that the resonant frequency increases almost linearly oped showing the relation between the effective capacitance of this
with the increase of glucose concentration in the phantom sam- curved plate sensing capacitor with the blood glucose concentration
ple but the impedance decreases nonlinearly with concentration in present in any of these fingers of a person. This model is supported
the frequency range from 10kHz-1MHz. A multi-sensor based non- by the low frequency works of different researchers (Li et al., 2018;
invasive glucometer technique (Geng et al., 2017) is developed where Chakraborty et al., 2015; Tura et al., 2010) as stated above, where it
low frequency and high frequency impedance spectroscopy tech- is shown that effective dielectric constant of blood sample decreases
nique & optical technique are used to estimate the glucose concen- linearly with the increase of glucose concentration. This linear rela-
tration. A differential Mueller matrix polarimetric technique (Phan tion is also observed in high frequency study (Liao et al., 2003) of
and Lo, 2017) is reported to measure the glucose concentration the effective dielectric constant of glucose solution. A modified op-
in human finger tip. The feasibility of the technique is established amp based capacitance measurement circuit has been developed to
from the study of rotation angle and depolarization index of tissue measure the glucose concentration in the blood of finger. The ac out-
phantom sample for the glucose concentration in the range from 0- put of the measuring circuit is converted into DC signal by using
500 mg/dl. It is observed that the rotation angle increases linearly precision rectifier and filter circuits, which is then input to a micro-
with increase of glucose concentration but the depolarization index controller through a suitable ADC unit. The microcontroller directly
decreases. The generation of ultrasonic wave in a glucose solution indicates the glucose concentration in engineering unit (mg/dl). The
by a photo acoustic excitation signal is utilized to develop a non- result thus obtained has been compared with the reading of a glu-
invasive blood glucose measurement technique (Zhao et al., 2017), cometer and it is observed that the two readings are almost identical.
where it is observed that the compressibility of the solution decreases The percentage error of the data obtained from the proposed tech-
with increase of glucose concentration. The calibration frequency of nique with respect to those obtained from glucometer technique is
online glucose monitors can be reduced by using Bayesian multi- found to lie within ±3.5%. The measurement has been carried out
day framework model (Acciaroli et al., 2017) and thus the accuracy in a number of persons. The experimental results are reported in the
and reliability of the sensor from less frequent data is increased. The paper. The characteristic curves are drawn by plotting the reading of
non-invasive impedance spectroscopy is combined with multiwave- proposed measurement system against the reading of a glucometer.
length NIR spectroscopy (mNIRS) in a multimodal spectroscopy A good linear characteristic has been observed.
IC (Song et al., 2015), where the impedance spectroscopy (IMPS)
circuit measures the dielectric parameters of tissues by using RLC
II. METHOD OF APPROACH
resonant circuit in which glucose level is estimated from resonant
impedance. The low frequency and high frequency impedance spec- The estimation of dielectric constant of a biological tissue by
troscopic study of glucose solution is also performed by a parallel direct measurement in vivo is very difficult. So the effective dielec-
plate capacitor type impedance network using glucose solution as tric constant of a biosample is generally estimated indirectly by using
the dielectric (Chakraborty et al., 2015) in the frequency range from a suitable capacitive transducer (Gun et al., 2017). So in the present
50 Hz to 4MHz. From this study, it is observed that the capacitance work, a modified capacitive transducer is designed using biological
of the parallel plate capacitor with the glucose solution as the dielec- tissue of finger as the dielectric material. The proposed transducer
tric nonlinearly depends on frequency of excitation signal. But at consists of two identical capacitive sensors, of which one capaci-
low frequency region near 1000 Hz, this variation is almost found tor is used as the sensing capacitor (CS ) with the biological tissue
to be linear. From the low frequency study of glucose solution by of the finger as the dielectric and the other capacitor is used as a
using an electromagnetic sensor (Tura et al., 2010), it is observed dummy capacitor (C0 ) with air as the dielectric. Each sensor consists
that the sensor output voltage decreases linearly with increase of of two identical semi-cylindrical curved copper plates fixed on a sil-
concentration of glucose in a sample solution having good similar- icon tube of suitable dimension by means of a thin layer of araldite
ities to human blood. The measurement accuracy of a non-invasive without any air gap. The thickness of silicon tube is selected to be
blood glucose concentration monitoring technique may be increased very small. The inner diameter and length of the silicon tube are

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-2


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Now the most part of the biomaterial present in the finger is water
whose dielectric constant is very high compared to the dielectric
constant of silicon tube material. Hence K 2 << K 1 . So the above
equation (2) may be approximated as

3K2 + 2f K1 2K1 f + 3K2


KS ≈ K1 [ ]= (3)
3K1 − f K1 3−f
or,
KS = a1 K1 + a2 K2 (4)
where
2f 3
a1 = ( ) and a2 = ( ) (5)
3−f 3−f
Hence from the theory of semi-cylindrical capacitor (Manaf and
Triyana, 2016), the capacitance of the sensor capacitor with finger
inserted into the silicon tube as shown in Fig. 1 is given by
ε0 KS A ε0 A
Cs = = (a1 K1 + a2 K2 ) (6)
π π
where A is the area of each semicylindrical curved copper plate.
Now for the dummy capacitor (C0 ), the finger is replaced by air
for which dielectric constant K 1 = 1. Hence the capacitance C0 of the
FIG. 1. (a) Schematic diagram of the proposed sensor. (b). Photographic view of dummy capacitor is given by
the proposed sensor.
ε0 A
C0 = (a1 + a2 K2 ) (7)
π
Now, let us consider the biological tissue material present in the fin-
so selected that any one of fore finger, middle finger and ring fin- ger is equivalent to two component living bio-mixture of which one
ger can be inserted into it without any air gap embracing its whole component is a non-living innert material like glucose and the other
length. There is a small gap of constant width between the curved component is the remaining part of the living tissue material consist-
copper plates in each side of every semi-cylinder capacitor as shown ing of water, muscle, bone and others present in the finger. Let the
in Figs. Figs. 1(a) & 1(b). From the copper plates, two lead wires are volume fraction of glucose present in this mixture be x, dielectric
brought out by rigid soldered joints. constant of glucose be K g and dielectric constant of the remaining
For the sensing capacitor CS with finger inserted into it, the part (mostly water) of the tissue be K w . So from the principle of com-
combinations of biological tissue present in the finger, silicon tube posite mixture solution (Qizheng and Jin, 2001; Liao et al., 2003), the
and thin layer of araldite together form a composite dielectric mate- effective dielectric constant K 1 of the biological tissue present in the
rial. Let the effective dielectric constant of this composite material finger may be given by,
be K S and volume fraction of finger inside the composite material
be f, permittivity of the biological tissue material present in finger K1 = (1 − x)Kw + xKg (8)
is ε1 and that of silicon tube material is ε2 and the effect of araldite
layer on the permittivity of composite material is negligible. So from From (6), (7) and (8), the ratio of the sensor capacitance (CS ) and
Bruggeman model (Sareni et al., 1997; Gun et al., 2017), the per- the dummy capacitance (C0 ) may be given by,
mittivity ε of the composite biosample material between the two CS (a1 K1 + a2 K2 ) a1 [(1 − x)Kw + xKg ] + a2 K2
electrodes is given by = =
C0 (a1 + a2 K2 ) a1 + a2 K2
3ε2 + 2f (ε1 − ε2 ) a1 Kw + a2 K2 a1 (Kw − Kg )
ε = ε1 (1) = − x = b1 − b2 x (9)
3ε1 − f (ε1 − ε2 ) a1 + a2 K2 a1 + a2 K2

Let the dielectric constant of the composite biomaterial of finger be where,


K 1 and that of silicon tube material be K 2 so that ε1 = ε0 K 1 , ε2 = ε0 K 2 a1 Kw + a2 K2 a1 (Kw − Kg )
and ε = ε0 K S where ε0 is permittivity of vacuum and K S is the dielec- b1 = and b2 = (10)
a1 + a2 K2 a1 + a2 K2
tric constant of the whole composite biosample material between the
electrodes. Hence the above equation is reduced to Since K w > K g always because at room temperature (25○ C), the value
of K g is about 2.5 and that of K w is about 78 - 80, so b1 and b2 are pos-
3K2 + 2f (K1 − K2 )
KS = K1 (2) itive real constants. Again the volume fraction (x) of glucose in the
3K1 − f (K1 − K2 ) living bio-sample material of the finger is mostly present in blood

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-3


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FIG. 2. Proposed non-invasive blood glucose monitoring


circuit.

as an aqueous solution. Hence from (9), it may be concluded that impedances of CS and C0 may be represented as, ZS = RS + 1
jωCS
and
the capacitance ratio of the proposed sensor capacitor and dummy Z0 = R0 + 1
jωC0
respectively where ω = 2πf is the angular frequency of
capacitor decreases linearly with concentration of glucose in blood.
sinusoidal source and f is the frequency. Hence for the non-inverting
In order to measure this capacitance ratio at low frequency, let
amplifier circuit consisting of op-amp A1 , the output voltage signal
us consider a following microcontroller based circuit as shown in
V 1 may be given by
Fig. 2.
In Fig. 2, CS denotes the capacitance of the proposed sensing Z0
capacitor of the finger as shown in Fig. 1 (a) and C0 denotes the V1 = (1 + )VS (11)
ZS
capacitance of the dummy air capacitor with exactly similar con-
struction as CS . The lead wires of sensing capacitors CS are con- or,
nected between circuit common and inverting terminal of op-amp ⎛ ⎞
1
R0 +
V1 = 1 +
jωC0
A1 and the lead wires of air capacitor C0 are connected between the VS (12)
same inverting terminal and output terminal of op-amp A1 i.e. in ⎝ RS + 1
jωCS

the feedback path of A1 . A stabilized sinusoidal oscillator of r.m.s
Now the loss components of sample capacitor CS and air capaci-
voltage V S at a low frequency of 1000 Hz is connected between cir-
cuit common and inverting terminal of op-amp A1 . Thus the circuit tor C0 are generally negligible. Hence at low frequency, ∣ jωC
1
S
∣ ≫
associated with op-amp A1 acts as a non-inverting amplifier giving a RS & ∣ jωC
1
0
∣ ≫ R0 . So the above equation may be reduced to
sinusoidal output ac voltage signal V 1 . The next part of the circuit is
a unity gain differential amplifier circuit with op-amp A2 where the CS
V1 = (1 + )Vs (13)
input ac excitation voltage signal (V S ) of non-inverting amplifier is C0
subtracted from its output voltage signal (V 1 ) so that at the output,
we get an ac voltage signal V 0 of op-amp A2 given by V 0 = V 1 − V S
Hence from (10) and (14), we have
for R1 = R2 = R3 = R4 . CS
V1 = (1 + )VS = (1 + b1 − b2 x)VS (14)
Now the output ac voltage signal V 0 of op-amp A2 and the exci- C0
tation signal V S are converted into ripple free dc signals V0′ and VS′
by using unity gain precision rectifier and filter circuits as shown by So the output signal V 0 of the unity gain differential amplifier circuit
block diagrams in Fig. 2. These dc output signals V0′ and VS′ of the with op-amp A2 and R1 = R2 = R3 = R4 is given by
rectifier and filter circuits are then input to a microcontroller circuit CS
through two analog input ports of two similar ADC units inbuilt V0 = V1 − VS = VS = (b1 − b2 x)VS (15)
C0
with the microcontroller circuit as shown in the block diagram in
Fig. 2. where CC0S denotes the effective gain of the measuring circuit. Since
Let the loss components of the sensing capacitor CS and that CS >> C0 , so the effective gain of the measuring circuit is high and
of the air capacitor C0 are represented by equivalent lump param- no additional amplifier is needed for further amplification of output
eter series resistances RS and R0 respectively so that the equivalent signal V 0 . Now V 0 and V S are converted into dc signals V0′ and VS′

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-4


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respectively by using rectifier and filter circuits. Hence V0′ and VS′ are microcontroller program. So a LCD display unit interfaced with the
proportional to V 0 and V S respectively so that the ratio VV0S = V0′ . Let
V′ microcontroller may be calibrated directly in terms of blood glucose
S concentration and the proposed technique thus acts as a noninva-
us assume this ratio to be y. Hence from (15), this ratio is given by
sive technique of measurement of glucose concentration in human
V0 V0′ blood. From experiment as explained in later section, the voltage sig-
y= = = b1 − b2 x (16) nals V0′ and VS′ are measured by using four and half digit multimeters
VS VS′
and blood glucose concentration (x) is measured by a commercial
Thus from the above equation, we may conclude that the value of glucometer (Accu-Chek Active). From blood glucose concentration
the ratio y = V0′ decreases linearly with increase of glucose con- characteristic drawn by plotting the ratio y = V0′ against glucose con-
V′ V′
S S
centration or volume fraction (x) of glucose in blood and may be centration x as shown in Fig. 5, it is observed that the voltage ratio
easily calibrated directly in terms of blood glucose concentration in a y = V0′ is related with blood glucose concentration by the following
V′
S
relation
y = 94.882 − 0.276x (17)
Thus from (16) and (17),
b1 = 94.882 and b2 = 0.276 (18)
Hence from (17), the glucose concentration x in human blood is
given by
y − 94.882
x= (19)
−0.276
From (19), the blood glucose concentration in human blood can be
easily calculated by a software program where the ratio y is calculated
from two input signals V0′ and VS′ in digital forms according to the
flowchart as shown in Fig. 3 in the next section.

III. DESIGN
The basic design of the proposed noninvasive technique is the
design of two identical capacitors of which one is used as the sensing
capacitor and the other is used as the dummy capacitor. Each capac-
itor consists of a hollow silicon tube of length 75 mm and thickness
2.5 mm, inner diameter 20 mm, outer diameter 25 mm so that any
one of the fingers except the thumb and the little finger may be just
inserted into the tube without any air gap as shown in Figs. 1(a) &
1(b). Each silicon tube is surrounded by two identical semicylindri-
cal curved clean copper plates. The copper plates are fixed on the
silicon tube by using very thin layer of araldite without any air gap
at the contact surface. There are two identical small gaps each of
about 4 mm between the two copper plates as shown Figs. 1(a) &
1(b). These copper plates are fabricated from two identical rectangu-
lar copper sheets so that identical gap lengths are obtained on both
sides. Two lead wires are brought out from the two copper plates
by rigid soldering at high temperature at the junction point. Before
soldering, both lead wire and the surface of the copper plate at the
junction are cleaned properly mechanically by scrubbing the surface
and using cleaning compound so that there is no possibility of dry
soldering between the connecting lead wire and the copper surface
at the junction. The lead wires constitute the terminals of the sens-
ing capacitor CS and air capacitor C0 . The electronic components
are mounted on a vero-board. The vero-board along with micro-
controller and LCD display unit is placed in a portable wooden box.
The air capacitor C0 is mounted inside this box and the lead wires of
the sensing capacitor CS are selected to have suitable length so that
the sensing capacitor may be rigidly fixed on the outside surface of
FIG. 3. Flowchart of the proposed software program.
the box at a suitable location where a finger can be easily inserted.

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-5


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The LCD display unit is also fixed outside the box so that on insert- LCD unit with I2C bus is procured from the market as a separate
ing the finger into the sensing capacitor silicon cylinder, the blood PCB unit.
glucose concentration may be directly indicated on the display unit. The software program of the microcontroller was designed
This indication is compared with the indicated blood glucose in a according to the following flowchart shown in Fig. 3. Since Arduino-
semi invasive type blood glucose measuring unit such as Accu-Chek Uno microcontroller board consists of 6 channels, 10 bit ADC units
Active-make glucometer manufactured by M/s Roche. The op-amps in the input voltage range from 0 to 5 volt, so its resolution is 5
A1 and A2 are selected as low noise OP07 and each of the resis- volt/1024 or 4.84 mV per unit. Hence input voltage V0′ in volt is con-
tors R1 , R2 , R3 , R4 is selected as 1 kΩ, half watt metal film resistor verted into digital mV signal by multiplying it with 4.84 as shown
with 1% tolerance. The supply voltage V S of the measuring circuit in the flowchart in Fig. 3. Now from (16), it is observed that with
is selected as a small stabilized sinusoidal signal of r.m.s value of 50 the increase of blood glucose concentration (x), the measuring cir-
mV. The rectifier and filter units are selected as ripple free precision cuit output voltage V0′ decreases and the digital count at ADC output
rectifiers with capacitive filters available in the market in the form decreases. So in order to maintain the indication within some upper
of PCB units. The microcontroller (ATMEGA-328P) with inbuilt 10 limiting value, a threshold count of 400 was selected in the above
bit ADC units mounted on a ready-made Arduino-Uno PCB avail- design of software program so that very high indication may not be
able in the market is used in the present design. The microcontroller treated as erroneous reading. This upper limit was selected by trial
output port is connected to a 16×2 LCD unit through I2C bus. The and error method during experiment. The glucose concentration is

FIG. 4. (a) Block diagram of the exper-


imental setup. (b) Photographic view of
the experimental setup.

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-6


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TABLE I. Experimental data for proposed transducer characteristic (V s = 50 mV, 1000 Hz).

Capacitance of the
proposed sensor
measured by LCR Output ac
meter before voltage (V0 )
Blood
connection in the of the proposed
Blood glucose
transducer circuit (pF) transducer in Volt Voltage ratio (y)
Room/body pressure level in
Date & temperature (mm Hg/ glucometer Middle Fore Ring Middle Fore Ring Middle Fore Ring
Person with age time ((○ C) mm Hg) (mg/dl) finger finger finger finger finger finger finger finger finger

2/2/2018, 18/35.5 118/80 80 22.6 22.6 22.6 3.65 3.65 3.65 73 73 73


10:05AM
2/2/2018, 18/35.5 120/82 90 21.5 21.5 21.5 3.50 3.50 3.50 70 70 70
11 AM
2/2/2018, 20/35.5 118/80 96 21 21 21 3.40 3.40 3.40 68 68 68
12 Noon
2/2/2018, 22/35.5 120/81 102 20.7 20.7 20.7 3.35 3.35 3.35 67 67 67
Person-1(Male), 1:00 PM
39yrs 2/2/2018, 25/35.5 118/78 145 19.6 19.6 19.6 2.75 2.75 2.75 55 55 55
2:00 PM
2/2/2018, 26/35.5 118/78 130 20 20 20 2.95 2.95 2.95 59 59 59
3:00 PM
2/2/2018, 25/35.5 120/81 118 20.5 20.5 20.5 3.10 3.10 3.10 62 62 62
3:50 PM
2/2/2018, 23/35.5 116/80 105 20.8 20.8 20.8 3.30 3.30 3.30 66 66 66
5:00 PM

directly displayed by designing the software program according to In the first part, the capacitance between lead wire terminals
(18) as shown in the flowchart in Fig. 3. (A & B) of the proposed capacitive sensor with clean and dry fin-
ger inserted into the sensor silicon tube without any air gap was
IV. EXPERIMENT measured in a selected person by a digital LCR meter (make: M/s
Motech industries Inc. Taiwan, model no.- MIC-4070D) in the pF
The experiment was performed with the experimental set up as
shown in the following block diagram in Fig. 4 (a) and photographic
view in Fig. 4 (b). The experiment was conducted in two parts as
stated below.

FIG. 5. Voltage ratio (y) versus blood glucose concentration (x) characteristic of FIG. 6. Percentage deviation curve of the proposed measuring circuit. From best
the proposed measuring circuit. fit linearity.

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-7


© Author(s) 2019
© Author(s) 2019
TABLE II. Comparison between experimental data obtained from proposed technique and those measured by conventional semi invasive glucometer.

Blood glucose
AIP Advances

concentration
Blood glucose
displayed in LCD
concentration
unit in mg/dl for % error observed for
B.P in Room/body displayed in
(mm Hg/ Date temperature Middle Fore Ring glucometer Middle Fore Ring
Person, age mm Hg) and Time (○ C) finger finger finger in mg/dl finger finger finger Remarks

115/70 5/2/2018 8A.M 20/35.8 85 84 85 87 2.29 3.44 2.29


121/78 5/2/2018 2 P.M 28/35.8 115 115 115 118 2.54 2.54 2.54

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059


118/80 6/2/2018 7:45AM 20/35.8 87 88 88 90 3.33 2.22 2.22 Data obtained
122/80 6/2/2018 2:30P.M 30/35.8 115 114 114 117 1.70 2.56 2.56 in both the
Person-2 (Male), 119/81 7/2/2018 7:50AM 17/35.8 90 89 90 91 1.09 2.19 1.09 techniques are
39yrs 123/80 7/2/2018 2:15PM 32/35.8 106 106 107 109 2.75 2.75 1.83 almost identical
118/78 8/2/2018 8:15AM 21/35.8 91 91 91 93 2.15 2.15 2.15 for person-2
124/82 8/2/2018 2:25PM 29/35.8 111 110 110 114 2.63 1.75 1.75
120/75 9/2/2018 8AM 17/35.8 89 88 89 92 3.26 4.34 3.26
120/76 9/2/2018 2:30PM 30/35.8 112 112 111 114 1.75 1.75 2.63

118/76 12/2/18 8:10AM 15/35.5 82 82 82 84 2.38 2.38 2.38


125/84 12/2/18 2PM 30/35.5 110 110 110 113 2.65 2.65 2.65
118/80 13/2/18 7:50AM 17/35.5 85 86 85 88 3.40 2.27 3.40 Data obtained
120/81 13/2/18 2:20PM 29/35.5 111 112 112 114 2.63 1.75 1.75 in both the
Person-3 (Male), 118/78 14/2/18 7:45AM 19/35.5 89 88 89 91 2.19 3.29 2.19 techniques are
22yrs 125/82 14/2/18 2:10PM 29/35.5 115 115 115 118 2.54 2.54 2.54 almost identical
116/76 15/2/18 8 AM 19/35.5 91 92 92 94 3.19 2.12 2.12 for person-3
121/81 15/2/18 2:25PM 28/35.5 116 116 117 120 3.33 3.33 2.50
118/80 16/2/18 8:30AM 16/35.5 94 95 94 97 3.09 2.06 3.09
123/79 16/2/18 2:30PM 28/35.5 126 126 126 128 1.56 1.56 1.56
ARTICLE

125/82 19/2/18 8:20AM 18/35.8 134 133 133 136 1.47 2.20 2.20
140/94 19/2/18 2:45PM 32/35.8 170 169 170 172 1.16 1.74 1.16
130/80 20/2/18 7:55AM 20/35.8 134 134 134 136 1.47 1.47 1.47 Data obtained
139/88 20/2/18 2:20PM 31/35.8 172 171 172 174 1.16 1.72 1.16 in both the
Person-4 (Male), 129/70 21/2/18 7:40AM 20/35.8 125 125 125 128 2.34 2.34 2.34 techniques are
58yrs 134/84 21/2/18 2:10PM 32/35.8 164 164 165 167 1.79 1.79 1.19 almost identical
128/82 22/2/18 8AM 21/35.8 121 120 122 124 2.41 3.22 1.61 for person-4
132/80 22/2/18 2:30PM 32/35 155 154 155 158 1.89 2.53 1.89
124/81 23/2/18 8:30AM 20/35.8 114 113 115 117 2.56 3.41 1.70
126/81 23/2/18 2PM 34/35.8 144 143 144 146 1.36 2.05 1.36
scitation.org/journal/adv

9, 105027-8
© Author(s) 2019
TABLE II. (Continued.)

Blood glucose
AIP Advances

concentration
Blood glucose
displayed in LCD
concentration
unit in mg/dl for % error observed for
B.P in Room/body displayed in
(mm Hg/ Date temperature Middle Fore Ring glucometer Middle Fore Ring
Person, age mm Hg) and Time (○ C) finger finger finger in mg/dl finger finger finger Remarks

102/62 26/2/18 8:35AM 22/35.5 84 85 85 87 3.44 2.29 2.29


108/72 26/2/18 2:25PM 34/35.5 104 105 105 108 3.70 2.77 2.77

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059


103/68 27/2/18 8:50AM 22/35.5 82 83 82 85 3.52 2.35 3.52 Data obtained
110/74 27/2/18 2:30PM 33/35.5 106 107 106 110 3.63 2.72 3.63 in both the
Person-5 (Female), 108/70 28/2/18 8:40AM 24/35.5 85 86 86 88 3.40 2.27 2.27 techniques are
21yrs 120/80 28/2/18 2:20PM 33/35.5 112 112 112 115 2.60 2.60 2.60 almost identical
110/70 8/3/18 8AM 19/35.5 90 91 91 94 4.25 3.19 3.19 for person-5
118/72 8/3/18 2:30PM 33/35.5 110 109 109 112 1.78 2.67 2.67
109/70 9/3/18 8:30AM 20/35.5 93 92 92 95 2.10 3.15 3.15
118/76 9/3/18 2:15PM 34/35.5 115 115 116 118 2.54 2.54 1.69

108/68 12/3/18 8:05AM 22/35 94 94 93 96 2.08 2.08 3.12


114/78 12/3/18 2:15PM 33/35 113 113 114 116 2.58 2.58 1.72
112/80 13/3/18 8:30AM 24/35 95 96 96 98 3.06 2.04 2.04 Data obtained
120/80 13/3/18 2:30PM 35/35 116 115 116 119 2.52 3.36 2.52 in both the
Person-6(Female), 115/75 14/3/18 8:10AM 23/35 91 91 90 93 2.15 2.15 3.22 techniques are
35yrs 119/81 14/3/18 2:25PM 37/35 114 115 115 118 3.38 2.54 2.54 almost identical
115/78 15/3/18 8AM 22/35 93 94 94 97 4.12 3.09 3.09 for person-6
121/80 15/3/18 2:30PM 35/35 116 115 116 118 1.69 2.54 1.69
110/75 16/3/18 7:50AM 26/35 95 94 95 98 3.06 4.08 3.06
121/79 16/3/18 2PM 31/35 113 114 113 116 2.58 1.72 2.58
ARTICLE

119/80 1/11/18 8:25AM 23/35.5 165 165 166 169 2.36 2.36 1.77
120/78 1/11/18 2:25 PM 32/35.5 240 241 240 245 2.04 1.63 2.04
118/80 2/11/18 7:45AM 24/35.5 155 155 155 158 1.89 1.89 1.89 Data obtained
123/80 2/11/18 2:20P.M 32/35.5 228 228 228 233 2.14 2.14 2.14 in both the
Person-7 (Male), 117/81 3/11/18 8:50AM 24/35.5 142 143 142 146 2.73 2.05 2.73 techniques are
45yrs 123/80 3/11/18 2:10PM 33/35.5 211 210 210 215 1.86 2.32 2.32 almost identical
118/78 6/11/18 8:10AM 25/35.5 138 138 138 141 2.12 2.12 2.12 for person-7
121/81 6/11/18 2:35PM 33/35.5 184 184 184 189 2.64 2.64 2.64
120/80 7/11/18 8AM 23/35.5 127 128 128 131 3.05 2.29 2.29
122/78 7/11/18 2:30PM 27/35.5 164 164 165 170 3.52 3.52 2.94
scitation.org/journal/adv

9, 105027-9
© Author(s) 2019
AIP Advances

TABLE II. (Continued.)

Blood glucose
concentration
Blood glucose
displayed in LCD
concentration
unit in mg/dl for % error observed for

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059


B.P in Room/body displayed in
(mm Hg/ Date temperature Middle Fore Ring glucometer Middle Fore Ring
Person, age mm Hg) and Time (○ C) finger finger finger in mg/dl finger finger finger Remarks

125/82 8/11/18 8:20AM 21/35 105 105 106 108 2.77 2.77 1.85
125/84 8/11/18 2:20PM 30/35 120 120 122 125 4.00 4.00 2.40
124/83 9/11/18 9:00AM 19/35 102 102 102 106 3.77 3.77 3.77 Data obtained
125/81 9/11/18 2:20PM 30/35 130 128 131 134 2.98 4.47 2.23 in both the
Person-8 (Male), 128/80 10/11/18 8:45AM 19/35 102 102 101 105 2.85 2.85 3.80 techniques are
60yrs 125/82 10/11/18 2:30PM 30/35 115 115 115 118 2.54 2.54 2.54 almost identical
126/81 13/11/18 8 AM 20/35 103 103 104 106 2.83 2.83 1.88 for person-8
125/81 13/11/18 2:15PM 31/35 116 118 117 121 4.03 2.47 3.30
125/80 14/11/18 8:30AM 20/35 98 98 100 102 3.92 3.92 1.96
126/79 14/11/18 2:30PM 31/35 124 124 124 128 3.12 3.12 3.12

119/80 15/11/18 8:10AM 22/35.8 87 87 87 90 3.33 3.33 3.33


118/78 15/11/18 2:45PM 32/35.8 112 112 112 116 3.44 3.44 3.44
120/78 16/11/18 8:55AM 23/35.8 90 91 90 92 2.17 1.08 2.17 Data obtained
120/80 16/11/18 2:40PM 33/35.8 114 114 115 118 3.38 3.38 2.54 in both the
Person-9 (Female), 120/75 17/11/18 8:40AM 23/35.8 87 88 87 90 3.33 2.22 3.33 techniques are
37yrs 118/78 17/11/18 2:20PM 30/35.8 112 110 112 115 2.60 4.34 2.60 almost identical
ARTICLE

116/80 21/11/18 8:55AM 20/35.5 92 92 93 95 3.15 3.15 2.10 for person-9


118/80 21/11/18 2:45PM 30/35.5 114 112 114 117 2.56 4.27 2.56
118/78 22/11/18 8:50AM 18/35.5 92 93 93 96 4.16 3.12 3.12
120/80 22/11/18 2:30PM 29/35.5 110 110 109 114 3.50 3.50 4.38
scitation.org/journal/adv

9, 105027-10
AIP Advances ARTICLE scitation.org/journal/adv

range before connecting the sensor in the proposed measuring cir- of commercial standard glucometer. These data were obtained under
cuit. Now the lead wires were connected with the measuring circuit the continuous supervision of a medical practitioner.
without the microcontroller section to determine the actual charac-
teristic of the transducer. The stabilized sinusoidal excitation source V. DISCUSSIONS
is selected at r.m.s voltage V s = 50 mV at low frequency 1000 Hz. From the voltage ratio characteristic of the proposed nonin-
This source was connected with the measuring circuit along with vasive blood glucose concentration measuring circuit as shown in
the dummy air capacitor (C0 ) in the feedback path of op-amp A1 Fig. 5, it is observed that the blood glucose concentration decreases
as shown in Fig. 2. Under this condition, the values of the rectified linearly with increase of concentration and follows the mathemat-
DC voltages V0′ and VS′ were measured by using four and half digit ically derived equation (16) to a very good extent. The percentage
digital multimeters. The ratio (y = V0′ ) of these two DC voltages deviation from linearity is also found to be small within ±2% of
V′
S
was determined. Now the actual blood glucose of the person was maximum span of best fit data as shown in Fig. 6. From this linear
measured by Accu-Chek Active glucometer by taking blood sam- characteristic equation, the software program of the microcontroller
ple from any other finger of the same or other hand. The experiment is designed as shown in the flowchart in Fig. 3.
From (15), the above voltage ratio ( VV0S = V0′ ) is equal to the
V′
was repeated for three fingers namely, middle finger, fore finger, ring
S
finger. The experimental data obtained from repetition of the exper- ratio of sensor capacitance CS to the dummy air capacitance C0 .
iment for the same person at different dates and times are shown in Since C0 may be assumed to be constant, so the sensor capacitance
Table I. CS also decreases linearly with increase of glucose concentration at
From above table, it is observed that the proposed sensor capac- low frequency. This linear behaviour of sensor capacitance at low
itance (CS ) was found to remain constant for insertion of three dif- frequency is also observed by many other workers such as Li et al.,
ferent fingers without air gap of any arm except thumb and little fin- 2018; Chakraborty et al., 2015; Tura et al., 2010. But the change of
ger. It is also observed that the variation of the effective capacitance sensor capacitance with change of blood glucose concentration is
of the proposed sensor with change of blood glucose concentration very small of the order of few pF as shown in Table I. So the con-
is very small of the order of few pF. But due to inherent gain ( CC0S ) of ventional capacitance bridge type or impedance type measurement
the measuring circuit, an appreciable change of output due to change may suffer from measurement error due to various effects such as
of blood glucose concentration is obtained. Now the characteristic stray capacitance effect, other conductor vicinity effect etc. More-
curve of the proposed sensor was drawn by plotting voltage ratio over, these measurement techniques require noise free signal con-
(y) against blood glucose concentration (x). A linear characteristic ditioner or amplifier circuit for measurement of blood glucose con-
graph is obtained as shown in Fig. 5. centration from capacitance measurement. In the proposed voltage
From this characteristic curve, the best fit characteristic equa- ratio measurement circuit, the noise factors associated with sensor
tion is determined by using MS Excel software program as shown in capacitance CS and dummy air capacitance C0 cancel each other in
Fig. 5. The best fit characteristic equation as shown in Fig. 5 above the proposed ratio measurement technique. Again the value of the
is found to be linear (y = 94.882 − 0.276x) The percentage deviation dummy air capacitance C0 is much less than the sensor capacitance
of the measured data from the best fit linear characteristic curve is CS and the output V 1 of the non-inverting amplifier circuit shown
found to be small as shown in Fig. 6. in Fig. 2 is in amplified form and no additional amplifier is needed
In the second part of the experiment, the experimental set up as to counteract the effect of small change of capacitor due to variation
shown in Figs. 4(a) & 4(b) was completed by connecting the output of glucose concentration.
terminals of the precision rectifier and filter circuits to the respective From the comparison of the measured data obtained from the
input ports of the ADC units of the microcontroller loaded with its proposed microcontroller based non-invasive blood glucose con-
software program designed according to equation (19). centration measuring circuit with those obtained from commercial
Now any one of clean & dry middle finger, fore finger, ring fin- glucometer as shown in Table II for various subjects, it is observed
ger of any arm of a particular selected person was inserted without that the measured data from the proposed noninvasive circuit are
any air gap into the sensing cylinder embracing the whole length of very close to the actual data obtained from glucometer. The per-
the sensor tube and the corresponding readings of the LCD display centage error of the measured data with respect to the glucometer
unit for blood glucose concentration in mg/dl were taken. Simulta- data is found to be within ±3.5%. Hence the proposed noninvasive
neously the actual value of blood glucose concentration was mea- measurement technique may be considered to have similar reliabil-
sured by the commercial standard glucometer (Accu-Chek Active) ity of measurement of blood glucose concentration in human blood
by collecting blood sample from another finger of the same or other like commercial glucometer having measurement error within ±8%.
arm of the person. Now blood pressure, body temperature of the per- But the main advantage of the proposed technique is that it is very
son along with room temperature were recorded. The experiment simple, less costly, completely noninvasive and painless with very
was repeated for three different fingers (middle finger, fore finger, much easier technique for continuous online study of a diabetic per-
ring finger) of the same person & different other persons at differ- son compared to the conventional non-invasive or semi invasive
ent times and dates. The corresponding indicated values of blood techniques.
glucose concentration in LCD unit along with the respective glu- The proposed technique may suffer from measurement error
cometer readings for eight different persons are recorded as shown due to the effects of various artefacts such as physiological condi-
in Table II. From this table, it is observed that the measured val- tion, ionic relaxation, blood pressure, temperature etc. These arte-
ues of blood glucose concentration by the proposed non-invasive facts tend to produce random inhomogeneous distribution of the
microcontroller based technique almost coincide with the readings components of the composite biomaterial as well as measurement

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-11


© Author(s) 2019
AIP Advances ARTICLE scitation.org/journal/adv

error. But Sareni et al., 1997 have shown that the effective permit- manufacturer’s data sheet. The technique of measurement used in
tivity of a composite material sample is not affected by the inho- the glucometer is completely different from the proposed technique.
mogeneous distribution of the components in the sample. Hence Hence it may happen that the measured value of blood glucose con-
the equations (1), (16) and (19) may be considered to have good centration by the proposed technique is smaller than that measured
reliability with respect to the proposed measurement technique. by the glucometer for the same subject under the same environment.
In the proposed work, the magnitude of the excitation signal So for a glucometer with good consistency, this type of measure-
was selected very small (50 mV, 1000 Hz) in order to avoid the satu- ment error should be continued for all observations as shown in
ration effect of op-amps. This small value signal is amplified due to Table II.
the presence of inherent gain factor CC0S of the measuring circuit. So Again it may be noted that the sample capacitance (CS =
no further amplifier circuit for the output signal V 0 has been used ε 0 KS A
π
= ε0πA (a1 K1 + a2 K2 )) as shown in (6) and air capacitance
before it is sent to rectifier and filter circuit. This helps in reducing (C0 = ε0πA (a1 + a2 K2 )) as shown in (7) should vary with variation of
further amplification of noise signal in the amplifier circuit thereby atmospheric parameters like humidity, temperature as well as other
producing better signal to noise ratio of the system. Again the vir- parameters. Here the effective lumped parameter dielectric constant
tually identical potentials of input terminals of op-amps A1 and K 1 of the bio-sample depends only on physiological conditions of
A2 reduce the effect of stray capacitance between the input termi- the sample but not on the atmospheric parameters. The effect of
nals. Thus noise signal due to stray capacitance effect is reduced. dielectric constant K 2 of the silicon tube material may be negligible
Moreover, the low pass filter circuit used at the output of each compared to that of K 1 . The atmospheric permittivity ε0 is depen-
rectifier unit further reduces the noise signal. Thus the signal dent on humidity and temperature of atmosphere. In the proposed
to noise ratio of the proposed technique may be assumed to be technique, the ratio CC0S is measured. So the effects of humidity and
improved. temperature may be assumed to be negligible since ε0 is cancelled
Since the resultant output given by (16) does not depend on out in the ratio measurement process. Moreover, both the glucome-
excitation signal, so it should not depend on frequency and form ter and the proposed measurement circuit are simultaneously used
factor of the excitation signal. In the present work, a stabilized sinu- under the same environment. Hence the measurement errors due to
soidal excitation signal (50 mV, 1000 Hz) has been used. During humidity and temperature may be identical or comparable in both
insertion of a finger inside the silicon tube, care should be taken so the techniques. Any moisture on the skin must affect the reading of
that the whole length of the sensor is embraced by the finger with no
the proposed system since moisture has large value of dielectric con-
air gap between it and the tube. This is because the air gap will pro-
stant. So during experiment, precautions should be taken so that the
duce an air capacitor connected in series with the sensing capacitor,
finger surface is completely dry without any moisture.
which will drastically affect the sensitivity of the sensor.
During experiment, it has been observed that a good contact
Since fore finger, middle finger and ring finger are of almost
between finger and probe without any air gap gives reliable read-
similar diameter, so during actual experiment, the insertion of these
ing which did not vary with the variation of contact pressure. This
fingers into the proposed sensor without any air gap has been
may be due to the fact that the variation of contact pressure does not
found to produce no appreciable change in reading of the proposed
produce any appreciable change of the glucose content in the sam-
measuring unit as shown in Table II.
ple blood. Again from (10) and (16), it is observed that the values
In the design of software program as shown in flowchart in
of b1 and b2 depend on dielectric constants of water (K w ), glucose
Fig. 3, a threshold value of 400 count of ADC output was arbitrar-
(K g ) and silicon tube material (K 2 ) along with the volume fraction
ily selected so that the indicated value of blood glucose may remain
within a maximum limiting value. This count 400 corresponds to (f ) parameters a1 and a2 shown in (5). Since the volume of silicon
400× 4.84 = 1936 mV at which y = 1936/50 = 38.72 and from equa- tube is constant and volume fraction (f ) does not depend on biolog-
tion (19), the blood glucose concentration x = (38.72-94.882)/-0.276 ical properties, so the parameters a1 and a2 may be assumed to be
= 203 mg/dl. This is the selected maximum range of the proposed independent of biological properties of the sample. The dielectric
measuring system. However for higher range, a threshold value less constant parameters K w , K g and K 2 are also independent of bio-
than 400 count may be easily selected in the software program. In the logical properties of bio-sample. Hence the parameters b1 and b2
software program, no minimum range is selected because it will cor- may be assumed to be constant being independent of the human
respond to maximum output V0′ of the measuring circuit. Now with subjects.
respect to the ADC unit, V0′ should always be less than 5 Volt by
selecting proper value of input supply which is selected as 50 mV in
the present work. If we consider the maximum value of V0′ at 5 Volt VI. CONCLUSIONS
or 5000 mV, at which y = 5000/50 = 100 and from equation (19), the A non-invasive blood glucose concentration measuring unit
blood glucose concentration x = (100-94.882)/-0.276 = -18.54 mg/dl. using a modified capacitive sensor has been designed and devel-
So a negative minimum indication of -18 mg/dl will be obtained. But oped in the present work. The developed microcontroller based
in practical case, this minimum value will not be possible and the blood glucose concentration measuring system has been found to
measuring circuit output will always remain at a value much below function satisfactorily and the measured values of blood glucose
5 Volt. As shown in Table I, this maximum value has been found to concentration of human blood are identical with those simultane-
be 3.65 Volt ac. ously measured by a conventional glucometer. In the present work,
It may be mentioned that the commercial glucometer with the ratio of measuring circuit output voltage signal to input excita-
respect to which the results of the proposed measuring circuit were tion signal has been theoretically and experimentally shown to be
compared, has about ±8% measurement error as mentioned in the linearly related with blood glucose concentration. The developed

AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-12


© Author(s) 2019
AIP Advances ARTICLE scitation.org/journal/adv

microcontroller based blood glucose concentration measuring unit Gun, L., Ning, D., and Liang, Z., “Effective permittivity of biological tissue:
operates on this linear relationship. Comparison of theoretical model and experiment,” Hindawi, Mathematical
Problems in Engineering 2017, 1–7.
Klonoff, D. C., “Noninvasive blood glucose monitoring,” Diabetes Care 20,
ACKNOWLEDGMENTS 433–437 (1997).
Li, J., Igbe, T., Liu, Y., Nie, Z., Qin, W., Wang, L., and Hao, Y., “An approach
The authors are thankful to the Department of Applied Physics, for noninvasive blood glucose monitoring based on bioimpedance difference
Instrumentation Engineering, University of Calcutta, the Depart- considering blood volume pulsation,” IEEE Access 6, 51119–51129 (2018).
ment of Electrical Engineering, Techno Main, Salt lake and the Li, J., Yang, D., Nie, Z., Liu, Y., and Wang, L., “Investigation of resonant fre-
Department of Electrical Engineering, Academy of Technology, quency and impedance for non invasive blood glucose monitoring,” Proceed-
Adisaptagram for providing the facilities to carry out this work. ings of the 7th Annual IEEE International Conference on Cyber Technology
in Automation, Control and Intelligent Systems, Hawaii, USA 1, 1649–1652
(2017).
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AIP Advances 9, 105027 (2019); doi: 10.1063/1.5116059 9, 105027-13


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