Opt Quant Electron (2018) 50:249

https://doi.org/10.1007/s11082-018-1520-2

High sensitivity and ultra‑compact optical biosensor

for detection of UREA concentration

Zaineb Gharsallah1 · Monia Najjar1,2   · Bhuvneshwer Suthar3 · Vijay Janyani4

Received: 16 November 2017 / Accepted: 29 May 2018

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract  In this paper, we suggest two-dimensional photonic crystal based biosensors

for measurement of urea concentration in urine by means of refractive index detecting.
In case of variation of urea concentration in urine, both the output peak intensity and the
resonant peak center wavelength will shift. Two different structure dimensions are used to
analyze the sensing characteristics of urine. The first sensor consists of a novel square ring
joined to a simple waveguide with rods in air configuration. The second sensor is schemed
by use of two-dimensional photonic crystals based on air hole in slab with elliptical reso-
nant cavity in the middle of a photonic crystal waveguide. To realize sensing in both cases,
we fill air area by urine sample. A high sensitivity is observed in small structures. In addi-
tion, we demonstrated a high quality factor, which is superior to those reported in recently
published work discussing urine components based on photonic crystal, with small size
sensors and fast response times.

Keywords  Photonic crystal · Optical biosensor · Ring cavity · Refractive index · Urine
concentration · Urea

* Monia Najjar
monianajjar@yahoo.fr
Zaineb Gharsallah
gharsallah.zaineb@hotmail.fr
Bhuvneshwer Suthar
bhuvneshwer@gmail.com
Vijay Janyani
vjanyani@mnit.ac.in
1
Communications Systems Laboratory (SysCom), National Engineering School of Tunis (ENIT),
University of Tunis El Manar (UTM), BP 37, 1002 Le Bélvédère, Tunisia
2
Higher Institute of Computer Sciences, University of Tunis El Manar (UTM), Tunis, Tunisia
3
Department of Physics, Government Engineering College, Bikaner, Bikaner 334004, India
4
Department of Electronics and Communication Engineering, Malaviya National Institute
of Technology, Jaipur, Rajasthan 302017, India

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1 Introduction

Research is constantly evolving to better detect our health disorder using bacteriological
examinations and biochemical tests. Generally, urine is subject of many tests and may
be used to detect the diseases by studying its regular and irregular components (Ahmad
2010). Normally, urine carries toxic waste of the body metabolism but this waste must
pursue standard quantities. Thus, its variation can mean a dysfunction of one organ or more
(Hypoglycemia-It’s Not All in Your Head, it’s All in Your Urine 2014). The results of pro-
tein degradation lead to a creation of urea, which must be eliminated by the kidney. The
presence of urea in urine indicates a pathology not only on the level of kidney but also
in the liver (Alamri) (Addis and Watanabe 1916). According to the data provided by the
World Kidney Day, 10% of the global community is affected by chronic kidney sickness
and as results of costly treatment; more than one million people decease every year (World
Kidney Day: “Chronic Kidney Disease” 2015). The cases of renal failure are expected to
rise in developing countries, including China, Pakistan, and India, where the total of aged
people is rising. Chronic kidney disease can be treated and diagnosed in early stage. Even,
the progress of kidney disease can be slowed or stopped. Moreover, liver disease estimates
are regularly rising beyond the years. Liver maladies have been arranged as the fifth main
reason of mortality based on a data provided by National Statistics in the UK (UK national
statistics). In addition, liver maladies are known as the second principal reason of death
between all diseases in the US (Everhart and Ruhl 2009).
To detect the existence of urea in urine, many ordinary techniques are available, sci-
entists have employed chemical reaction coupled colorimetric and fluorometric detec-
tion methods (Francis et al. 2002; Searle 1984; Mitic et al. 2011; Srivastava et al. 2007;
Coulombe and Favreau 1963). All these techniques need many chemical reagents, many
steps and complex stages of sample preparation. Consequently, experimental error can be
introduced.
Since the discovery of the sensor based on optic system by Clark and Lyons, the poten-
tials of photonic crystals (Phc) have been exploited in extremely compact and sensitive
optical sensors (Sharma and Sharan 2014, 2015; Robinson and Dhanlaksmi 2017; Guda-
gunti et al. 2014; Sharan et al. 2014). According to the technology expansion of photonic
crystals production, new design schemes of optical sensors may be proposed, and designed.
Optical biosensor elements have been subject of research interest, and still today new tech-
nologies for different applications like medical area, military and environmental monitor-
ing. The application of bio sensing has achieved a great interest within the last two dec-
ades. It includes biosensor to find out glucose concentration in urine (Sharma and Sharan
2014, 2015; Robinson and Dhanlaksmi 2017), detection of DNA, breast cancer (Gudagunti
et al. 2014), pregnancy test, and cancer cell detection (Sharan et al. 2014).
For a healthy human body, the amount of urea in urine ranges between 60 and 100 mg/
dl in collection done irregularly (Ahmad 2010). The urine urea check is used to evalu-
ate protein fail in a human’s body to detect the protein ingestion and to assess the kid-
ney function. Abnormal urea levels are often indicators of various diseases including
liver disease, renal disease, hereditary urea cycle abnormalities, heart failure, or dietary
problems (Marescau et  al. 1997; Thomas and Morgan 1979; Aronson et  al. 2004). The
reduced quantity of urea excreted by kidney, which is found in severe Diabetic mellitus
cases, denotes a kidney trouble and malnourishment. The high rate of urea presents a sign
of an excess of protein intake, protein breakdown and kidney damage (Henry 1974; Bishop
et  al. 2013). Therefore, it is of great necessity to develop high-sensitive urea sensor for

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accurate measurement of urea concentration and for ensuring that the concentration is safe
for human health. In this paper, we designed two-dimensional photonic crystal based bio-
sensor for measuring refractive index and detecting urea concentration in urine. Two differ-
ent structures are used to analyze the sensing characteristics of urine. In Sect. 2, we firstly
discuss the sensor based on a novel micro cavity design based on square micro cavity with
rods in air configuration. Then, we analyze the sensor based on air hole in slab with a new
form of resonant cavity. The obtained simulations and results are discussed and compared
in Sect. 3. Finally, Sect. 4 concludes the paper.

2 Sensor design

From (Ahmad 2010), it is clear that physical property of urine, specifically, refractive
index, specific gravity, and surface tension, are very sensitive to the urea concentration
(Table  1). For normal human health, the standard value of urea resides in urine ranges
between 60 and 100 mg/dl in random collection.
Urine is the fluid treated by the kidneys. It is a subject to a process of filtration, secre-
tion, and reabsorption. Consequently, its compositions are adapted with a healthy amount.
It includes a large quantity of water that organic and inorganic chemicals are thawed such
as albumin, creatinine, bilirubin, glucose, and urea. Dietary intake, physical, activity endo-
crine function, and metabolism are the main causes that can induce a change in the concen-
tration of urine components. The irregular glucose concentration indicates a diabetes mel-
litus. Many Biosensors based on photonic crystal discussed the concentration of glucose in
urine (Robinson and Dhanlaksmi 2017; Sharma and Sharan 2015). The uncommon level of
urea excreted by the kidney is an index of kidney malfunction, high consumption, and high
protein loss. Nevertheless, the concentration of albumin and bilirubin does not significantly
influence the refractive index of the urine and the changes in the refractive index of the
urine are only in the range of 1.335 ± 0.001. From the available database (Ahmad 2010),
our investigated sensor can detect the existence of urea in the urine with high sensitivity
coefficient.

2.1 Sensor 1

Our proposed device, which is a photonic crystal biosensor, is able to measure the urea
component of urine. A schematic design of the suggested biosensor is depicted in Fig. 1.
The investigated structure is a Photonic crystal waveguide (PhcW1) with square micro cav-
ity placed in the center. It consists of a square lattice of silicon rods with refractive index
­nsilcon = 3.46, lattice constant a = 558  nm and rod radius R = 111.6  nm. The square micro
cavity is realized by increasing the radius of defected holes, whose radii are defined as

Table 1  Urea concentration in Sample UREA concentration in Refractive index

urine and its correspondence urine
refractive index
A Normal 1.335 ± 0.001
B 0.625 gm/dl 1.337 ± 0.002
C 1.25 gm/dl 1.338 ± 0.002
D 2.5 gm/dl 1.339 ± 0.001
E 5 gm/dl 1.342 ± 0.001

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Fig. 1  Schematic design of Sensor1 and its band diagram

­R1 = 2*R. To achieve a very high output intensity, the rod’s radius in the center of micro
cavity is chosen to be equal to R.
The band diagram of basic structure without any defect is plotted in Fig. 1; it represents
the range of transverse electric (TE) photonic band gap (PBG). Only one PBG occurs in
the structure from 0.259 to 0.375 which is corresponding to wavelength ranges covering
the third windows of optical communication spectrum.

2.2 Sensor 2

The second biosensor structure consists of circular air holes in silicon slab triangularly
arranged with lattice pitch a = 372  nm and hole’s radius r = 111.6  nm. The Phc resonant
cavity is obtained by removing a single row of holes and adding an elliptic hole in the
center of waveguide. To achieve a very high output intensity, the horizontal and vertical
radii of the resonant cavity are chosen to be equal to R1 = 558  nm and R2 = 148.8  nm,
respectively.
Figure 2 shows the band gap diagram (TM) of the second basic structure without defect,
it represents the range of two transverse magnetic photonic band gaps. Nevertheless, we
will focus only on the photonic band gap limited between 0.259 and 0.375 as it covers the
third optical communication window.

Fig. 2  Schematic design of Sensor2 and its band diagram

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Fig. 3  Transmission spectrum of Sensor1 for various urea concentrations

Table 2  Characteristics of Sensor1 
Cases UREA concentra- Refractive index of Resonance wave- Normalized output Q.F
tion in urine sample length (nm) intensity

A Normal 1.335 ± 0.001 1593.6 0.99156 570

B 0.625 gm/dl 1.337 ± 0.002 1594 0.99109 560
C 1.25 gm/dl 1.338 ± 0.002 1594.2 0.99002 550
D 2.5 gm/dl 1.339 ± 0.001 1594.4 0.98867 510
E 5 gm/dl 1.342 ± 0.001 1595.1 0.97892 520

3 Simulation results and discussion

In this paper, Rsoft software is used to simulate the transmission spectrum of the proposed
photonic crystal sensors. The refractive index of urine alters with the variation of urea con-
centration. Mostly, when the refractive index of a photonic crystal structure changes, the
output peak intensity or the resonant wavelength or both of them, will be shifted.
In case of Sensor1, the approach of output intensity change is studied. Figure 3 plots the
transmission spectrum for various concentrations of urea in urine as indicated in Table 1.
It is sighted that the intensity in the output port is reduced whereas the urea concen-
tration in urine is raised. Contrary, the resonant wavelength is increased. At the ordinary
healthy situation, resonant wavelength, normalized output intensity, and Quality fac-
tor of our studied sensor divining in the urea concentration are 1593.6  nm, 99.1%, 570,
respectively.
It is seen that despite the slightness of refractive index variation, which is about 0.001,
there is a shift of 0.05822 in the output intensity. Consequently, the studied device namely
Sensor1 has a high sensitivity. The various urea concentrations in urine and its refractive
index, resonant wavelength, normalized output intensity, and Quality factor of Sensor1 are
listed in Table 2.
As indicated in Table  2, we noticed a change in the output intensities because of the
urine refractive index variation according to various urea concentration levels in urine. It

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Fig. 4  Time response of Sensor1  1.0

0.9

0.8

Monitor Value (a.u.)

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0
0 200 400 600 800 1000
cT (µm)

Fig. 5  Transmission spectrum of Sensor2 for various urea concentrations

is evident that our sensor would be of great use to differentiate between urine samples with
low, normal, or high urea concentration.
The output power level for Sensor1 (Fig.  4), the output power reaches its maxi-
mum value 0.9 after CT = 600  µm, which corresponds to the detection response time
T = 600/C = 2 ps. This value can be considered as very low compared to published results.
Furthermore, Sensor1 has very compact size equal to 8.4 × 4.4  µm2. These important
performances: small sensing time, high sensitivity and ultra-compact size are main advan-
tages of photonic crystal sensors to use over the conventional chemical testing method.
To demonstrate the operating principle of Sensor2, and to evaluate its sensitivity, we
calculated the output spectrum Sensor2 by using the same approach of resonant wave-
length change. Figure 5 plots the transmission peak for various concentrations of urea in
urine as indicated in Table 1.
It is shown that the resonance wavelength is increased with the urea concentration
rising, while, the resonant peak is decreasing. For normal healthy situation, resonance

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Table 3  Characteristics of Sensor2 
Cases UREA concentra- Sample’s refractive Resonance Normalized output Sensitivity
tion in urine index of wavelength intensity

A Normal 1.335 ± 0.001 1542.7 0.99442 550

B 0.625 gm/dl 1.337 ± 0.002 1543.8 0.99295
C 1.25 gm/dl 1.338 ± 0.002 1544.4 0.99294 600
D 2.5 gm/dl 1.339 ± 0.001 1545 0.99207 600
E 5 gm/dl 1.342 ± 0.001 1546.6 0.98891 533

Fig. 6  Time response of Sensor2  1.0

0.9

0.8
Monitor Value (a.u.)

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0
0 200 400 600 800 1000
cT (µm)

wavelength, normalized output intensity, and sensitivity of Sensor2 divining in the urea
concentration are 1542.7 nm, 99.4%, 550, respectively.
It is seen that although the slightness variation of refractive index, which is about
0.001, there will be a shift of 0.6 nm in the resonant wavelength. Consequently, Sensor2
has a very high sensitivity.
The various urea concentrations in urine and its refractive index, resonant wave-
length, normalized output intensity and Quality factor of Sensor2 are listed in Table 3.
By distinguishing the output power or resonance wavelength of the Sensor2, the
respective urea concentration can be known. Accordingly, we can guess the health issues
and kidney status. The studied sensor has a small size around 5.6 × 2.9 µm2 which needs
small quantity of samples to detect the regarded parameters. In addition, the response
time of Sensor2 is very brief (Fig. 6).
The sensing time is calculated for a constant output power. In Fig.  6, the curve
reaches a constant value when CT = 120  µm. Therefore, the optimum sensing time is
equal to 0.4 ps.
As a comparison, we resume in Table 4 the performance characteristics of proposed
sensors and published results (Sharma and Sharan 2015; Robinson and Dhanlaksmi
2017).
From Table 4, Sensor2 offers the highest sensitivity and the smallest size. However,
Sensor1 provides the highest Quality Factor comparing with published work.

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Page 8 of 10

Table 4  Comparison table
References Author name Urine component Q factor Sensitivity Size (µm2) Resonance wave- Output power
length (nm)

Sharma and Sharan (2015) Poonam et al. Glucose *** *** *** *** 0.348
Robinson and Dhanlaksmi (2017) Robinson et al. Urea 264 *** 11.4 × 11.4 1585 1
Sensor1 Present work Urea 570 *** 8.4 × 4.4 1593.6 0.99
Sensor2 Present work Urea *** 550 5.6 × 2.9 1542.7 0.99
Z. Gharsallah et al.
High sensitivity and ultra‑compact optical biosensor for… Page 9 of 10  249

For practical aspect, the hole diameter (Sensor1) and the space between rods (Sensor2)
are about 200 nm which is an appropriate dimension to contain the urea molecule having
size in order of 3.2 angstrom (0.32 nm) (KARIM).

4 Conclusion

Photonic crystal with defect is considered as a promising approach for biosensors devices
regarding its ability to detect and analysis data in a short time. In this work we proposed
two biosensors based on Phc structures. For the first proposed sensor, the results showed
that detecting urea concentration in urine could be possible with a very high sensitivity. In
addition, it is configured with size 8.4 × 4.4  µm2 where quality factor and response time
are 570 and 2 ps respectively. For the second sensor, very high sensitivity around 550 and
a short response time around 0.4 ps are demonstrated in small size 5.6 × 2.9 µm2. There-
fore, these two sensors are perfect devices for biomedical application. Due to its flexibility,
adaptability and capability to integrate with smart material, photonic crystal based sensor
figuring as a new breakthrough concept of high technology and presenting a great candi-
date for medical domain.

Acknowledgements  The authors wish to acknowledge the Centre for Science and Technology of the Non-
Aligned and Other Developing Countries, India for the scholarship grant.

References
Addis, T., Watanabe, C.: A method for the measurement of the urea-excreting function of the kidneys. J.
Biol. Chem. 28(1), 251–259 (1916)
Ahmad, S.I.: Studies on some biophysical aspects of human renal excretory fluid. In: Ph.D dissertation.
Department of Physics, JNTU, Hyderabad, India (2010)
Alamri, A.: Estimation of serum urea and urine urea
Aronson, D., Mittleman, M.A., Burger, A.J.: Elevated blood urea nitrogen level as a predictor of mortality in
patients admitted for decompensated heart failure. Am. J. Med. 116(7), 466–473 (2004)
Bishop, M.L., Fody, E.P., Schoeff, L.E.: Clinical Chemistry: Principles, Techniques, and Correlations. Lip-
pincott Williams & Wilkins, Philadelphia (2013)
Coulombe, J., Favreau, L.: A new simple semimicro method for colorimetric determination of urea. Clin.
Chem. 9(1), 102–108 (1963)
Everhart, J.E., Ruhl, C.E.: Burden of digestive diseases in the United States part II: lower gastrointestinal
diseases. Gastroenterology 136(3), 741–754 (2009)
Francis, P.S., Lewis, S.W., Lim, K.F.: Analytical methodology for the determination of urea: current prac-
tice and future trends. TrAC Trends Anal. Chem. 21(5), 389–400 (2002)
Gudagunti, F.D., Sharan, P., Talabattula, S., Nainitej, V.: Early stage detection of breast cancer using hybrid
photonic crystal ring resonator. In: 2014 International Conference on Advanced Communication Con-
trol and Computing Technologies (ICAC​CCT​), pp. 1542–1545. IEEE
Henry, J.: Todd, Sanford, Davidsohn:” Clinical Diagnosis and Measurement by Laboratory Methods”. WB
Saunders and Co, Philadelphia (1974)
Hypoglycemia-It’s Not All in Your Head, it’s All in Your Urine. http://180de​greeh​ealth​.com/hypog​lycem​ia-
%E2%80%93-it%E2%80%99s-not-all-in-your-head-it%E2%80%99s-all-in-your-urine​/ (2014). Accessed
17 July 2014
KARIM, A.: Faculte de Pharmacie
Loichot, C., Grima, M.: Faculté de Médecine de Strasbourg. Module de Pharmacologie Générale DCEM1
2006 (2005)
Marescau, B., Nagels, G., Possemiers, I., De Broe, M.E., Becaus, I., Billiouw, J.-M., Lornoy, W., De Deyn,
P.P.: Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insuffi-
ciency. Metabolism 46(9), 1024–1031 (1997)

13
 249   Page 10 of 10 Z. Gharsallah et al.

Mitic, S.S., Miletic, G.Z., Kostic, D.A., Rasic, I.D.: A spectrophotometric study of streptomycin effect on
the clinical urea determination. Chin. J. Chem. 29(1), 135–142 (2011)
Robinson, S., Dhanlaksmi, N.: Photonic crystal based biosensor for the detection of glucose concentration in
urine. Photonic Sens. 7(1), 11–19 (2017)
Searle, P.L.: The Berthelot or indophenol reaction and its use in the analytical chemistry of nitrogen. A
review. Analyst 109(5), 549–568 (1984)
Sharan, P., Bharadwaj, S., Gudagunti, F.D., Deshmukh, P.: Design and modelling of photonic sensor for
cancer cell detection. In: 2014 International Conference on the IMpact of E-Technology on US (IMPE-
TUS), pp. 20–24. IEEE
Sharma, P., Sharan, P.: Photonic crystal based ring resonator sensor for detection of glucose concentration
for biomedical applications. Int. J. Emerg. Technol. Adv. Eng. 4(30), 702–706 (2014)
Sharma, P., Sharan, P.: Design of photonic crystal-based biosensor for detection of glucose concentration in
urine. IEEE Sens. J. 15(2), 1035–1042 (2015)
Srivastava, T., Althahabi, R., Garg, U.: Measurement of urea nitrogen and creatinine concentrations in peri-
toneal dialysate and other body fluids using the Vitros analyzer. Clin. Biochem. 40(5), 420–422 (2007)
Thomas, R., Morgan, B.: Increased production of urea and heart failure. BMJ 2(6193), 795 (1979)
UK national statistics. http://www.stati​stics​.gov.uk/. Accessed 7 Nov 2017
World Kidney Day: “Chronic Kidney Disease”. http://www.world​kidne​yday.org/faqs/chron​ic-kidne​y-disea​se
(2015)

13