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High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low

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Article in Photonic Sensors · January 2023

DOI: 10.1007/s13320-023-0675-z

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PHOTONIC SENSORS / Vol. 13, No. 2, 2023: 230202

High-Sensitivity Early Detection Biomedical Sensor for

Tuberculosis With Low Losses in the Terahertz Regime
Based on Photonic Crystal Fiber Technology
Nazmi A. MOHAMMED1, Omar E. KHEDR2,3*,
El-Sayed M. EL-RABAIE3, and Ashraf A. M. KHALAF4
1
Department of Electronics and Communication Engineering, Medina Higher Institute for Engineering and Technology,
Giza 12947, Egypt
2
Department of Communications and Electronics, Alexandria Higher Institute for Engineering and Technology,
Alexandria 21311, Egypt
3
Department of Electronics and Communications Engineering, Faculty of Electronic Engineering, Menoufia University,
Menouf 32952, Egypt
4
Department of Communications and Electronics, Faculty of Engineering, Minia University, Minia 61111, Egypt
*
Corresponding author: Omar E. KHEDR E-mail: omar.khedr@aiet.edu.eg

Abstract: Tuberculosis is one of the most contagious and lethal illnesses in the world, according to
the World Health Organization. Tuberculosis had the leading mortality rate as a result of a single
infection, ranking above HIV/AIDS. Early detection is an essential factor in patient treatment and
can improve the survival rate. Detection methods should have high mobility, high accuracy, fast
detection, and low losses. This work presents a novel biomedical photonic crystal fiber sensor, which
can accurately detect and distinguish between the different types of tuberculosis bacteria. The
designed sensor detects these types with high relative sensitivity and negligible losses compared to
other photonic crystal fiber-based biomedical sensors. The proposed sensor exhibits a relative
sensitivity of 90.6%, an effective area of 4.342×10–8 m2, with a negligible confinement loss of
3.13×10–9 cm–1, a remarkably low effective material loss of 0.013 2 cm–1, and a numerical aperture of
0.346 2. The proposed sensor is capable of operating in the terahertz regimes over a wide range
(1 THz – 2.4 THz). An abbreviated review of non-optical detection techniques is also presented. An
in-depth comparison between this work and recent related photonic crystal fiber-based literature is
drawn to validate the efficacy and authenticity of the proposed design.
Keywords: Tuberculosis; photonic crystal fiber; relative sensitivity; terahertz; confinement loss; effective area

Citation: Nazmi A. MOHAMMED, Omar E. KHEDR, El-Sayed M. EL-RABAIE, and Ashraf A. M. KHALAF, “High-Sensitivity
Early Detection Biomedical Sensor for Tuberculosis With Low Losses in the Terahertz Regime Based on Photonic Crystal Fiber
Technology,” Photonic Sensors, 2023, 13(2): 230202.

among the most important platforms used in ODP

1. Introduction
applications and for making them cost-effective [1].
Photonic crystals (PhCs) have become an PhCs, in this type of application, are compared to
attractive choice for optical data processing (ODP) famous photonic-based technologies, such as visible
applications. In recent years, they have been ranked light communications (VLC) [2–8], semiconductor
Received: 8 July 2022 / Revised: 28 October 2022
© The Author(s) 2023. This article is published with open access at Springerlink.com
DOI: 10.1007/s13320-023-0675-z
Article type: Regular
Page 2 of 16 Photonic Sensors

optical amplifiers (SOAs) [9], fiber Bragg grating PCF types have been designed and manufactured for
(FBG) [10–12], Mach-Zehnder interferometer (MZI) that purpose, such as chemical sensors [42],
[13, 14], free-space optical communication (FSO) temperature sensors [43], pressure sensors [44],
[15, 16], and modulators used in optical networks salinity sensors [45], and blood component sensors
[17]. Characteristics obtained from the photonic [46].
domain, including immunity to electromagnetic In recent decades, scientists paid a lot of attention
interference, safety in highly combustible to the terahertz radiation band [47, 48]. Terahertz
environment, fast response speed, and long-range emission can be transmitted across optical fibers and
monitoring, are features that make PhC promising poses no threat to human health [36]. Therefore,
[18, 19]. Additional merits are low power optical fiber-based sensors that operate in terahertz
consumption, flexibility in structural design, and frequencies have been proposed and used in different
excellent sensitivity measurement [20]. As a result, real-life activities. Based on the aforementioned
today, PhCs are frequently utilized in several ODP merits of PCFs, a wide range of PCF-based
technologies, such as resonators [21], couplers [22], biomedical sensors were designed, tested, and
channel drop filters [23], optical modulators [24], sometimes fabricated. Some examples are blood
oscillators [25], switches [26], logic gates [27], component sensor [46], glucose concentration sensor
adders [28], subtractors [29], encoders [30], and [49], malaria detection sensor [50], protein detection
sensors. [51], and sensors for different types of cancers [52,
Recently, PhCs-based sensors have been 53]. The most important PCF-sensing features
considered among the most promising photonic- (sometimes referred to as performance evaluation
based sensing techniques. Their exceptional physical parameters) include relative sensitivity (RS),
properties, such as reflectance/transmittance and confinement loss (CL), effective material loss (EML),
increased sensitivity, are important factors for future operating speed frequency, effective area (Aeff),
sensing methods [31, 32]. In the last decade, PhCs numerical aperture (NA), and fabrication possibility
have been used to provide accurate, real-time, and using currently available technologies [54–56].
cost-effective photonic-based sensors [33–35]. According to the worldwide tuberculosis report
Photonic crystal fibers (PCFs) are direct issued by the World Health Organization (WHO) in
applications that utilize the advantages of PhCs in 2021, every year, 10 million people become infected
optical fibers. Due to their various capabilities, PCFs with tuberculosis (TB) [57]. Despite the fact that
are getting tremendous attention from scientists in the tuberculosis is a preventable and curable disease, 1.5
field of optics. The primary aspect of PCFs, as optical million people die from it each year, making it the
waveguides, is the revolutionary methodology that world’s leading infectious killer [57]. TB is the
they used for light propagation [36–38]. PCFs are greatest cause of death among human
preferable to alternative optical channels because of immunodeficiency virus (HIV) patients, as well as a
their durability, compact size, high tensile strength, significant contributor to antibiotic-resistant bacteria.
and inexpensive cost [36, 39]. Also, design flexibility, TB is a contagious disease that is the primary cause
single-mode propagation, high confinement, of illness and death globally. TB was the top
propagation in air and solid core, and controllable infectious agent-related cause of mortality,
birefringence are extra advantages of PCFs [40, 41]. surpassing Acquired Immunodeficiency Syndrome
In addition to providing electromagnetic signal HIV/AIDS [57]. In 2019, the most recent year during
propagation interactions with liquids and gases, PCFs which the WHO published worldwide death
can be used in many sensing applications. Several estimates by cause, TB was the 13th largest cause of
Nazmi A. MOHAMMED et al.: High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low Losses Page 3 of 16
in the Terahertz Regime Based on Photonic Crystal Fiber Technology

death worldwide and the leading infectious results, specifications, and sensing characteristics of
agent-related cause of death [57]. In its last issued the new design are presented in Section 4.
report on TB, the WHO predicted that in 2020, the Verification of this work’s sensing capabilities is
disease was going to be the second biggest infectious proven through an in-depth comparison with related
agent-related cause of death [57]. It also estimated photonic biomedical sensors in Section 5. Finally, a
that in 2020, ten million people would have been conclusion that includes the value of the proposed
infected with the TB [57]. There are 5.6 million men, sensor’s performance and characteristics is drawn in
3.3 million women, and 1.1 million children Section 6.
diagnosed with TB around the world [57]. In this
2. Sensor structure design
same report, it was expected that, in 2020, the
number of fatalities of TB would increase, and The cross-sectional structure of the proposed PCF
previous declines in the annual number of sensor is introduced in Fig. 1. Teflon, zeonex, silica,
tuberculosis cases would be slow down dramatically and topas are the most popular materials utilized as
[57]. There were fewer TB diagnoses and treatments, the background for terahertz-based PCFs, due to their
as well as TB preventive treatment, in 2019 than in excellent characteristics and lower absorption loss
2018 [57]. Modeling forecasts indicate that the compared to other optical material sensors [36].
disruptions induced by the pandemic could have a Zeonex has a minimum absorption loss of 0.2 cm−1,
significantly greater impact on the number of persons limited water absorption, high transparency,
contracting tuberculosis and dying from the disease increased glass transition temperature, and excellent
in 2022. In conclusion, continuous and serious efforts optical stability following exposure to humidity and
should be done to design, test, and, if possible, heat. Hence, it is chosen as the sensor’s background
fabricate then deliver to the medical field several material [58, 59].
devices, sensors, and machines that deal with such
impairments. Furthermore, if these efforts are
dedicated to meet early detection mechanisms, the
outcomes would be attractive and useful. Early
detection techniques must satisfy several
requirements. Examples are high sensing accuracy, PML

low operating losses, low power consumption, Zeonex

compact devices, and high response speeds. Air

Analyte
This work presents a serious attempt to meet the
majority of the aforementioned requirements. A PCF
Fig. 1 Cross-sectional view of the proposed tuberculosis
sensor proposed is designed, simulated, and sensor.
evaluated. Key performance evaluation parameters, A detailed view of the proposed sensor’s
such as RS, CL, EML, Aeff, and NA, are also structure, including geometrical parameters, is shown
addressed. A comparison with related PCF-based in Fig. 2. This detailed cross-sectional view shows
techniques is achieved to confirm the novelty of the that a single circular air hole with a radius (X) is
proposed design. drilled into the core, which will contain the sample of
The remainder of this article is organized as analyte cells. The cladding region starts from the
follows: the sensor structure design is presented in inner circle with a radius C1, which measures 100 µm
Section 2. Section 3 discusses the performance and ends with the outer circle radius (C2), which
evaluation parameters of the proposed sensor. The measures 440 µm. The thickness of the clad’s outer
Page 4 of 16 Photonic Sensors

circle (t) is equal to 20 µm. The cladding region cladding region. Geometrical parameters are
consists of twelve symmetric syllables of air holes summarized in Table 1.
placed in the cladding section. It also has 12 strips of Table 1 Geometrical parameters values of the proposed
length (L) which contain 12 similar rectangular air sensor.

holes. The width of the strip is denoted by (W1) and is Parameter Description Value (µm)

equal to 35 µm. The rectangular air hole inside the X Core radius 85
strip has a width of W2 and a length of W3, with values C1 Clad’s inner radius 100
of 20 µm and 25 µm, respectively. The distance C2 Clad’s outer radius 440
between each rectangular air hole is denoted by W4 t Clad’s outer circle thickness 20
and is equal to 10 µm.
L Length of the strip 340
Finally, the rectangular air holes are located at the
W1 Width of the strip 35
center of the strip at a distance of 5 µm from the wall
W2 Width of the rectangular air hole 20
of the strip. At the outer area of the presented sensor,
W3 Length of the rectangular air hole 25
a perfectly matched layer (PML) boundary condition
Distance between rectangular air hole
is used. Its major role is to absorb the light signal W4
and each other
10

escaping from the core and traveling towards the Distance between the rectangular air
W5 5
cladding, preventing reflection back towards the core. hole and the wall

Its radius is 10% of the outermost circle of the

L(340 μm)
X W5 (5 μm)
C1
(100 μm)

t(20 μm) W4
W 1 W3
(35 μm) (10 μm) (25 μm)
C2
(440 μm)

W5 (5 μm) W2 (20 μm)

Fig. 2 Geometrical parameters of the proposed sensor.

Nowadays, numerous fiber fabrication sensors [65]. However, the proposed structure may
techniques, which are used to manufacture PCF require an accurate fabrication procedure. The
sensors, are commercially available, such as sol-gel proposed sensor structure was designed and
[60], capillary stacking [61], stack and draw [62], 3D simulated using the COMSOL Multiphysics software
printing [63], and extrusion [64]. Since the proposed (version 5.6). Its optical properties were analyzed by
sensor PCF includes square and rectangular air holes, using the finite element method (FEM). This method
the 3D (3-dimensional)-printing method is the best is more accurate than other well-known numerical
option for fabrication. The 3D printing method has approaches [66]. The meshing process was
been effectively utilized to fabricate symmetries performed using in a finer mesh, with a total of
structures. In recent years, the Max Planck Institute 22 130 domains and 3 472 boundary elements, as
has manufactured a variety of complex-shaped PCF shown in Fig. 3.
Nazmi A. MOHAMMED et al.: High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low Losses Page 5 of 16
in the Terahertz Regime Based on Photonic Crystal Fiber Technology

is as small as possible. Equation (2) is used to

calculate EML [56, 67]:
 ε0 

2
 nmat E α mat dA 
μ0 mat
EML =   (cm −1 ) (2)
 0.5 ( E × H ) zdA 
 all
ˆ

 
where H represents the intensity of the magnetic field
in the z-direction, E represents the intensity of the
Fig. 3 Finer mesh of the proposed sensor. electric field in the z-direction, and ε0 and μ0 represent
3. Performance evaluation parameters the permittivity and permeability of free space,
respectively. The background material refractive
To evaluate the effectiveness of detection of the
index is denoted as (nmat), and αmat represents the
proposed PCF sensor, as well as its ability to meet the
absorption loss of the substance.
early detection requirements previously indicated,
Aeff is another important feature. The electric field
different evaluation parameters should be used to
distribution (E) must be inserted into the core for the
analyze the sensor’s performance. For biomedical
single-mode propagation. Any PCF-based sensor’s
sensing applications, relative sensitivity (RS),
effective area measures its significant detecting
confinement loss (CL), effective material loss (EML),
region. Aeff is determined by (3) [56, 67]
operating speed frequency, effective area (Aeff), and
(  E )
2 2

numerical aperture (NA) are considered as the dx dy

Aeff = (μm 2 ) . (3)
characteristic parameters. The efficiency of a
biomedical sensor is determined by these features.
(  E 4
dx dy )
NA represents the variety of incident light angles
For PCF-based sensors, the light must propagate
that the fiber transmits and receives. NA is a unitless
mainly in the core region and be heavily confined to
value that depends on light velocity (c), effective area
the core.
Aeff, and frequency (f). For sensing applications, a
The CL property is utilized to determine light’s
greater NA is recommended, which can be obtained
confinement in the core region. It represents the light
by decreasing Aeff. The value of NA is determined by
that passes from the core to the cladding region due to
(4) [56, 68]:
the finite number of air holes. Equation (1) is utilized
1
in the calculation of CL [56,67]: NA = . (4)
 4π f  π f 2 (Aeff )
1+
 × Im ( neff ) (cm )
−1
CL =  (1) c2
 c 
where f represents the resonant frequency, c RS is the primary optical characteristic that
represents the velocity of light, and Im(neff) effectively addresses sensing capability. The
represents the effective refractive index’s imaginary percentage of RS estimates the power that passes
value. through the core relative to the total power inserted.
EML is the quantity of energy absorbed per unit Equation (5) is utilized to determine the value of RS
length by the background material. Loss of the [56, 68]:
molecules of the material will contribute to the
dissipation of some optical power, such as heat. EML

 Re( Hy Ex − Hx Ey ) dxdy  n 
 sample
RS =    *100%
r (5)
should be minimal, if the PCF model is properly   Re( Hy Ex − Hx Ey ) dxdy  neff 
constructed, and the area of the background material  all  
Page 6 of 16 Photonic Sensors

where nr represents the refractive index of the others optimization parameters are tested, but this is
tuberculosis infected samples, and neff is the real the one chosen). This is done for several reasons. The
component of the effective refractive index. Ex and Ey first is that a large number of tissue cells is required
represent the electric fields in x and y polarizations, for accurate sensing. Secondly, an optimization of all
respectively. Hx and Hy represent the magnetic fields evaluation parameters (i.e., EML, CL, operating
in x and y polarizations, respectively. speed frequency, Aeff, NA, and RS) is required for
every tissue cell tested. Finally, it will be shown that
4. Results and discussion
the outcome of these intensive optimization
It is important to state that the design stages of the process/trial methods will be utilized to find the
sensor will mainly depend on the accuracy optimum value for the radius that will lead to the best
measurement of the refractive index (RI) of normal performance evaluation parameters. All numerical
cells and those infected with several types of analyses are calculated for a frequency range of
mycobacterium tuberculosis. RIs of normal and 1.0 THz to 2.4 THz and are computed with COMSOL
several samples infected with different types of Multiphysics (version 5.6). The performance of each
mycobacterium tuberculosis are shown in Table 2, of the evaluation parameters will be presented
which will be used to indicate the sample’s status separately in the following sub-sections.
[69–71]. Each precise refractive index measurement
4.1 Effective material loss (EML)
will be associated with a particular type of normal or
infected sample, as shown in Table 2. Figure 4 illustrates the EML of the proposed
Table 2 RIs of cells infected with several types of
sensor for detecting different tuberculosis-infected
tuberculosis. samples, as a function of the frequency range from
Tuberculosis samples RI 1 THz to 2.4 THz. EML can be calculated from (2), as
indicated in Section 3. EML versus frequency shows
Normal blood plasma (NPS) 1.351
that EML starts to decrease from 1 THz to 2 THz for
TB1 1.343
all samples. From 2 THz to 2.2 THz, EML is nearly
Cells infected with several
TB2 1.345 constant. After 2.2 THz, EML starts to slightly
types of tuberculosis
TB3 1.347 increase once more for all tuberculosis-infected
samples. This means that 2.2 THz is the optimum
TB4 1.348
frequency for operation, in respect to EML, for all
Several optimization techniques and trial samples. Meanwhile, Fig. 5 shows the variation of
methods are usually applied to the PhC/PCF-based EML with respect to variations in a core radius (X), in
sensor designs to find the optimum values for the order to find the optimum X. X will vary from 85µm
operating characteristics or evaluation parameters. to 125 µm. This clearly shows that the minimum
Examples are adjusting the radius of the holes [35, EML occurs at X of 115 µm, making this the optimum
72], examining various values of the cavity’s radius value.
[30], varying the background material [73], setting The numerical values at an X of 115 µm and a
different distances for the displacement between the frequency of 2.2 THz for EML are found to be as
main cavity/cavities and the origin of the lattice [74, follows: 0.013 286 for normal blood plasma, and
75], and varying the core radius [36]. 0.014 019, 0.013 831, 0.013 647, and 0.013 556 for
This work will assume that adjusting the radius of samples infected with different tuberculosis bacteria,
the core is the main optimization parameter (i.e., i.e., TB1, TB2, TB3, and TB4, respectively.
Nazmi A. MOHAMMED et al.: High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low Losses Page 7 of 16
in the Terahertz Regime Based on Photonic Crystal Fiber Technology

90.3% for samples infected with different types of

0.020
TB1
tuberculosis, i.e., TB1, TB2, TB3, and TB4,
0.018
respectively.
EML (cm–1)

TB2
0.016
TB3
0.014
TB4 95

Relative sensitivity (%)

0.012 TB1
NPS
0.010 90 TB2
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
85 TB3
Frequency (THz)
TB4
Fig. 4 EML of the proposed sensor for various samples 80
NPS
infected with tuberculosis versus frequency.
75
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
0.04 Frequency (THz)

TB1 Fig. 6 RS of the proposed sensor for various samples

0.03 infected with tuberculosis versus frequency.
EML (cm–1)

TB2
0.02 TB3
TB4 95
0.01 Relative sensitivity (%) TB1
NPS
90 TB2
0
85 90 95 100 105 110 115 120 125 85 TB3
X (μm) TB4
Fig. 5 EML of the proposed sensor for various samples 80
NPS
infected with tuberculosis versus X at 2.2 THz. 75
85 90 95 100 105 110 115 120 125
4.2 Relative sensitivity (RS) X (μm)

Figure 6 illustrates the variation of RS within the Fig. 7 RS of the proposed sensor for various
tuberculosis-infected samples versus X at 2.2 THz.
frequency range from 1 THz to 2.4 THz, for various
tissue samples infected with tuberculosis. As 4.3 Effective area (Aeff)
previously indicated, (5) provides the formula for Aeff versus frequency of the suggested
calculating RS. RS starts to increase from 1 THz to tuberculosis sensor is shown in Fig. 8. This graphical
1.8 THz, for all tissues samples. From 1.8 THz to representation shows that Aeff decreases with
2.4 THz, it is almost constant for all infected samples. increments in frequency within the range of 1 THz to
Since RS is constant for frequencies higher than 2.4 THz, for all samples infected with tuberculosis.
1.8 THz, 2.2 THz is chosen to be the optimum Despite that the 2.4 THz is the optimum value for the
frequency for all tissue samples, regarding this effective area, the change in Aeff between 2.2 THz to
parameter. 2.4 THz is very small and can be neglected. The
On the other hand, Fig. 7 illustrates the variation change is nearly about 0.15×10–8 m2. So, for the
in RS relative to X. This is performed in order to find continuity of the superior advantages in both relative
the best value for X, which will achieve the optimum sensitivity and effective material loss at 2.2 THz. The
value for RS. X will vary from 85µm to 125 µm. Its frequency of 2.2 THz is still remaining the optimum
optimum value is found to be 115 µm. For X values operating frequency for the proposed sensor.
higher or lower than 115 µm, the values of RS are less Figure 9 presents the variation in Aeff relative to X.
than expected. The graphical representation shows an increase in Aeff,
For an X of 115 µm and a frequency of 2.2 THz, as X increases from 85µm to 115 µm. From 115 µm to
RS values are found to be as follows: 90.6% for 125 µm, Aeff for all tuberculosis-infected samples
normal blood plasma and 89.9%, 90.1%, 90.2%, and slightly decreases by 0.1×10–8 m2, which brings X to
Page 8 of 16 Photonic Sensors

115 µm, the optimum radius for the proposed design. in the values of CL for all tuberculosis-infected
The numerical values for Aeff at X of 115 µm and samples between 2.2 THz and 2.4 THz is nearly
a frequency of 2.2 THz are found to be as follows: around 10–1 or less, which can be neglected to ensure
4.35×10–8 m2 for normal blood plasma, and the aforementioned advantages.
4.34×10–8 m2, 4.342×10–8 m2, 4.343×10–8 m2, and The feature of CL versus frequency has been
4.344×m2 for infected samples of different types of examined at different X starting from 85µm to
tuberculosis, i.e., TB1, TB2, TB3, and TB4, 125 µm, same as RS, EML, and Aeff. Figure 11
respectively. illustrates the variation of CL for X from 85µm to
125 µm, at a frequency of 2.2 THz. CL sees its
9×10−8
9×10−8
minimum value for all tuberculosis-infected samples
8×10−8 8×10−8
at an X of 115 µm. This makes the value of 115 µm
Effective area (m2)

TB1
7×10−8
TB2
7×10 −8 6×10−8
5×10−8 TB3
for X optimum for most of the evaluation parameters.
The numerical values for CL, at an X of 115 µm
−8
4×10
TB4
6×10−8 3×10−8
2×10−8 NPS
1×10−8 and a frequency of 2.2 THz, are found to be as
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
Frequency (THz) follows: 3.13×10–9 for normal blood plasma and
Fig. 8 Aeff of the proposed sensor for various
tuberculosis-infected samples versus frequency.
4.83×10–9, 4.34×10–9, 3.89×10–9, and 3.68×10–9 for
samples infected with different types of tuberculosis,
5×10−8 i.e., TB1, TB2, TB3, and TB4, respectively.
TB1 1.00×10−10
Effective area (m2)

4×10 −8 TB2 1.00×10−9 TB1

1.00×10−8
Confinement loss (cm–1)

TB3 TB2
1.00×10−7
3×10−8 TB4
1.00×10−6 TB3
NPS 1.00×10−5
TB4
2×10−8 1.00×10−4
85 90 95 100 105 110 115 120 125
1.00×10−3 NPS
X (μm)
1.00×10−2
Fig. 9 Aeff of the proposed sensor for various 1.00×10−1
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
tuberculosis-infected samples versus X at 2.2 THz. 1.00×10−0
Frequency (THz)
4.4 Confinement loss (CL) Fig. 10 CL of the proposed sensor for various
tuberculosis-infected samples versus frequency.
Figure 10 presents the variation in CL versus
frequency. It can be seen that CL decreases as 1.00×10−10

frequency increases for all tuberculosis-infected

Confinement loss (cm–1)

TB1
samples from 1 THz to 2.4 THz. Thus, the linearity 1.00×10−9 TB2
behavior is obvious for all samples, within this TB3

frequency range. However, a non-linearity behavior 1.00×10−8

TB4

occurs after 2.4 THz. Despite this issue, the minimum NPS
85 90 95 100 105 110 115 120 125
CL for all tuberculosis-infected samples is found to 1.00×10−7

occur at 2.4 THz. As such, 2.2 THz is chosen as the Frequency (THz)

optimum frequency for the proposed sensor, for three Fig. 11 CL of the proposed sensor for various
tuberculosis-infected samples versus X at 2.2 THz.
reasons. The first reason is to ensure that the
4.5 Numerical aperture (NA)
frequency will be within the linear region of CL. The
second reason is to ensure the continuity of the NA is another essential photonic characteristic
superior values for both RS, EML, and Aeff, which that mainly depends on Aeff and frequency. NA
occur at 2.2 THz. The third reason is that the variation reflects the ability of the fiber to keep light and other
Nazmi A. MOHAMMED et al.: High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low Losses Page 9 of 16
in the Terahertz Regime Based on Photonic Crystal Fiber Technology

0.42
waves confined within it without dispersion. To
attain a high numerical value for NA, the RI of the 0.40 TB1

Numerical apreature
core must be greater than that of the cladding. 0.38 TB2

Figure 12 presents the relationship between NA TB3

0.36
and the operating frequency of various tuberculosis- TB4
0.34
infected samples. NA is reduced, as frequency NPS

increases because it is inversely proportional to it. 0.32

85 90 95 100 105 110 115 120 125
NA should be as high as possible (i.e., up to a certain X (μm)
limit, to permit single-mode operation only). So, in Fig. 13 NA of the proposed sensor for various
tuberculosis-infected samples versus X at 2.2 THz.
order to maintain single-mode operation, the
allowable range for NA should be from 1.4 THz to
2.4 THz. Since there is no significant difference
between 2.2 THz and 2.4 THz, the optimum operation
frequency is chosen to be 2.2 THz, due to the
aforementioned advantages gained at 2.2 THz.
On the other hand, Fig. 13 represents the variation
in NA versus X in various tuberculosis-infected (a) (b)
samples. It clearly shows that NA decreases as X
increases. The slight change in NA between an X of
85 µm and 115 µm is negligeable. Thus, for the sake
of the previously stated benefits related to evaluation
parameters (i.e., RS, EML, CL, and Aeff) at an X of
115 µm, this value is chosen as the optimum X.
The numerical values for NA, at an X of 115 µm (c) (d)
and a frequency of 2.2 THz, are found to be as
follows: 0.346 2 for normal blood plasma and
0.346 4, 0.346 3, 0.346 3, and 0.346 2 for samples
infected with different types of tuberculosis, i.e.,
TB1, TB2, TB3, and TB4, respectively. Figure 14
represents the electric field distribution for various
tuberculosis-infected samples, at the optimum
(e)
frequency of 2.2 THz and the optimum X of 115 µm. Fig. 14 Distribution of the electric field for different brain
tissue samples at 2.2 THz: (a) NPS, neff =1.310 8; (b) TB1, neff
=1.312 5; (c) TB2, neff =1.314 3; (d) TB3, neff =1.315 2; (e) TB4,
0.55 neff =1.317 9.
TB1
Numerical apreature

0.50
TB2 5. Comparison with related literature and
0.45
TB3 non-optical detection techniques
0.40
TB4
0.35 NPS
5.1 Non-optical detection techniques
0.30 The goal of this section is to review the famous
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4
Frequency (THz) commercial detection techniques for the different
Fig. 12 NA of the proposed sensor for various
tuberculosis samples with their advantages,
tuberculosis-infected samples versus frequency. disadvantages, and cost. This should provide an
Page 10 of 16 Photonic Sensors

insight view of the promising features of the blood test “interferon-gamma release assays
proposed design, especially when merged with the (IGRAs)”. All have their limitations, such as a chest
following sub-section (i.e., 5.2). x-ray alone is inconclusive; the TST lacks specificity
Traditional tuberculosis tests are either inaccurate and reliability. These methods can be improved by
or take too long to complete [76, 77]. Additionally, a merging with other techniques such as artificial
rapid and reliable diagnostic approach that intelligence [78, 79], it will considerably boost their
distinguishes between active and latent tuberculosis capabilities. Table 3 shows a comparison between
infections is absent. The current standard diagnostic different non-optical techniques to detect
tests for tuberculosis are as follows: the chest x-ray tuberculosis with their merits, disadvantages, and
examination (CXR), tuberculin skin test (TST), and cost.
Table 3 Non-optical detection techniques with a price range, advantages, and disadvantages [80–83].

Technique Advantages Disadvantages Price

(1) Reduced operating expenses (1) It generates 2-dimentional (2D) images of 3D systems
(2) Enhanced image quality with the ability to enlarge (2) There is a reader-to-reader modification
(3) Reduced dose of radiation (3) The specificity is low, because no abnormality is conclusive of
(4) Enhanced portable systems suitable for use with tuberculosis
mobile units (4) There is a total absence of a universally accepted reporting
The chest (5) The possibility of computer-aided detection, system 8$
x-rays without human interference (5) Ionizing radiation is used to detect diseases USD
(CXR) (6) Enhanced (digital) archiving ability (6) There is a requirement for specialized equipment (with an [84]
(7) The capability of transmitting images online adequate input power supply)
(7) The machine must be operated and the results interpreted by
qualified staff
(8) Limited access in rural areas
(9) There is only a limited amount of hard copy archiving
(1) Inexpensive (1) Appropriate placement of the TST into the skin requires skilled
(2) Used for over a century with lots of experience staff
(3) Individuals with the following medical problems are (2) After a 48- to 72-hour incubation period, a second clinic visit is
preferred in this test: diabetes mellitus, chronic renal required
failure (3) Since inter-reader and intra-reader fluctuation is common, a 3$–13$
Tuberculin skin test
(4) Easy to conduct skilled technician is required to read and interpret the TST result USD
(TST)
(4) Sensitivity is reduced, particularly in people with compromised [85]
immune systems
(5) A positive TST result does not necessarily indicate the presence
of the mycobacterium tuberculosis bacteria in the body at the time of
testing
(1) Achieves greater sensitivity and specificity (1) The test should be performed by a qualified operator in a
(2) Only one clinic consultation is required laboratory environment
Blood test
(3) Can provide results in less than 24 hours; (2) High cost 35$–40$
(interferon-gamma
(4) Relies on an immunological response based on (3) More laboratory resources required USD
release assays,
relatively short-lived T-effector cells; (4) Depends on the complicated process of lymphocyte separation [85]
IGRAs)
(5) A positive result implies that the immune system (5) Lack of prospective studies
has recently been exposed to the M TB bacteria

5.2 Comparison with related literature identifying samples infected with different types of
This section will present an in-depth comparison tuberculosis, as well as normal uninfected samples,
between this work and other studies that explores using photonics-based sensing techniques, especially
different types of biosensors, using PCF techniques. PCFs.
Before starting, it should be mentioned that there is a Table 4 presents a comparison between the
serious shortage in the field of sensing and literature related to PCF-based biosensors and this
Nazmi A. MOHAMMED et al.: High-Sensitivity Early Detection Biomedical Sensor for Tuberculosis With Low Losses Page 11 of 16
in the Terahertz Regime Based on Photonic Crystal Fiber Technology

work. This research demonstrates the novelty of advantages of this material are previously covered in
introducing a biomedical sensor, with attractive Section 2.
features, which can detect different types of To ensure the smooth production of the proposed
tuberculosis bacteria, using a PCF platform. The design, it is important to evaluate the impact of the
most promising feature in the proposed design is its fabrication tolerances. In the standard fabrication
RS. The design proposed in this work provides a procedure, 2% tolerance is allowed in global
90.6% RS, which is considered as a key feature. The parameters. Since the rectangular holes in the strip
ultra-high-speed operation, which is an inherent will be challenging to be fabricated using the current
characteristic of all photonic-based sensing
technology, it will be varied by ±2% and investigate
techniques (as indicated in Section 4), especially in
its effect on the evaluation parameters. The
PCF-based ones, is clear in this work. The widest
performance of the proposed PCF sensor with ±2%
possible operating frequency range (1 THz – 2.4 THz)
variations shows that RS varies from 90.6% to 88.9%
is also achieved in this study. From this work’s
at its lowest value. However, CL varies by nearly
results and discussion, which can be seen in Section 4,
2.2 THz is found to be the optimum value for the around 10–1 below its value. EML varies from 0.013 2
accurate sensing operation. The use of zeonex, as the in its original value to be 0.008 2. Aeff and NA are
background material for this design, is an advantage, almost the same without any affect to the ±2%
as it is in one other sensor, as seen in Table 4. The change in the rectangular holes in the strip.
Table 4 Comparison between the proposed tuberculosis sensor and biosensors based on photonic crystal fiber.

Detection Operating Background RS EML

Ref. Aeff CL NA
target frequency (THz) material (%) (cm–1)
[86]
Cancers – Silica – – – –
2018 209.12 dB/m
[87] Blood
1.5 Topas 1.55×105 µm2 80.93 – – –
2019 Components
[88] Blood
1.0 Topas 1.86×105 μm2 87.68 1.86×10–9 cm–1 – –
2021 Components
[89]
Biosensor 1.0 Topas ̶ 82.26 5.84 ×10–8 dB/m – –
2020
[90]
Biosensor 0.8–3 Zeonex 1.32×10–7 m2 88.36 5.55×10–8 dB/m 0.006 99 –
2021
[91]
Biosensor 0.8–1.4 Topas 1.1×10–7 m2 – 5.42×10–13 dB/cm 0.066 0.518
2019
[92]
Biosensor 1 Zeonex 1.24×105 μm2 87.02 1.95×10–3 cm–1 0.009 –
2020
[93]
Biochemical 1–2 Zeonex 97 657 μm2 77.71 2.8×10–11 cm–1 0.004 8 –
2021
[94]
Chemical 1.14 TOPAS 1.39×105 μm2 70 10–11 cm–1 – 0.557
2020
[95] Blood
– Silica – 66.46 8.134 3×10–11 dB/cm – –
2019 components
[68]
Chemical 1.6 Silica 69 800 μm2 85.7 1.7×10–9 cm–1 – 0.372
2017
[96]
Chemical 2.0 Zeonex 1.5×105 μm2 85.80 1.62×10–9 cm–1 0.023 –
2018
This
Biosensor 1–2.4 Zeonex 4.342×10–8 m2 90.6 3.13×10–9 cm–1 0.013 2 0.346 2
Work
Page 12 of 16 Photonic Sensors

The proposed design has a remarkable of the Creative Commons Attribution 4.0 International
License (http://creativecommons.org/licenses/by/4.0/),
performance in Aeff, which is found to be which permits unrestricted use, distribution, and
4.342×10–8 m2, the optimum value among all reproduction in any medium, provided you give
biosensors, as indicated in Table 4. This is a key appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons license, and
factor when integrating this biosensor with other indicate if changes were made.
medical/diagnostic systems currently in use.
Regarding the performance of the losses, the
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