sensors

Review
Microwave Sensors for Breast Cancer Detection
Lulu Wang 1,2 ID

1 Department of Biomedical Engineering, School of Instrument Science and Opto-Electronics Engineering,

Hefei University of Technology, Hefei 230009, China; [email protected]
2 Institute of Biomedical Technologies, Auckland University of Technology, Auckland 1142, New Zealand

Received: 31 January 2018; Accepted: 20 February 2018; Published: 23 February 2018

Abstract: Breast cancer is the leading cause of death among females, early diagnostic methods with
suitable treatments improve the 5-year survival rates significantly. Microwave breast imaging has
been reported as the most potential to become the alternative or additional tool to the current gold
standard X-ray mammography for detecting breast cancer. The microwave breast image quality is
affected by the microwave sensor, sensor array, the number of sensors in the array and the size of the
sensor. In fact, microwave sensor array and sensor play an important role in the microwave breast
imaging system. Numerous microwave biosensors have been developed for biomedical applications,
with particular focus on breast tumor detection. Compared to the conventional medical imaging and
biosensor techniques, these microwave sensors not only enable better cancer detection and improve
the image resolution, but also provide attractive features such as label-free detection. This paper
aims to provide an overview of recent important achievements in microwave sensors for biomedical
imaging applications, with particular focus on breast cancer detection. The electric properties of
biological tissues at microwave spectrum, microwave imaging approaches, microwave biosensors,
current challenges and future works are also discussed in the manuscript.

Keywords: lab-on-a-chip; label-free; breast cancer; microwave sensor; microwave imaging

1. Introduction
Cancer is a major public health issue worldwide and the second leading cause of death in the
United States [1]. In 2017, 1,688,780 new cancers and 600,920 cancer deaths occur in the United States [1].
To date, there is no clear reason why people get cancer, but some factors may increase cancer risk, such
as tobacco, obesity, lack of physical activity, alcohol, infections, genetic and molecular mechanisms [2].
Clinical studies showed that early diagnostic methods with suitable treatments improve the 5-year
survival rates significantly [3]. Lung cancer, breast cancer, prostate cancer, liver cancer, colorectal
cancer and stomach cancer are the most common types of cancers [4], and breast cancer is the leading
cause of cancer death among females in the United State [5].
Biopsy-based methods are normally used to identify cancerous tissue and benign tissue [6],
however, such techniques suffer from high cost and require trained people [7]. Over the past decades,
biosensor-based methods to detect cancer have attracted the interest of many people [8–13]. A biosensor
normally contains target cancer marker, bioreceptor and compatible biotransducer components that
play an imperative role and decide the technical specifications of the biosensor device. More recent
studies have investigated Lab-on-chip based biosensors for cancer detection due to their high selectivity,
sensitivity and specificity [14–16]. Additionally, they have the advantages in biological sample
processing, high throughput, low reagent and sample consumption, short assay time, and multiplexed
detection [17]. The development of lab-on-chip sensor was envisioned to be a useful tool for better
understanding of cancer metastasis. It is urgently needed to develop a high sensitivity and label-free
method for early rapid diagnosis of breast cancer. A number of biomarker-based methods have been
studied for breast cancer detection [18–21], including radioimmunoassay, immunohistochemistry,

Sensors 2018, 18, 655; doi:10.3390/s18020655 www.mdpi.com/journal/sensors

Sensors 2018, 18, 655 2 of 17

enzyme-linked immunosorbent assay, and fluoroimmunoassay. However, the biomarker-based

methods have some disadvantages include expensive, time-consuming, require complex labeling
process and trained people, and often limited in detection sensitivity [22]. To date, cancer biomarker
discovery is still in its discovery stage and the evidence is too restricted to apply biomarker-based
methods as the diagnostic tools for early breast cancer detection [23]. For example, protein biomarkers
cannot be used as individual biomarkers for identifying of breast cancer as a single marker does not
provide sufficient information to confirm the cancer type, and the obtained information is related to
the stage of cancer, treatment and the state of subjection.
Apart from biomarker-based methods, screening-based diagnostic techniques are the commonly
used methods in hospitals to identify diseases such as breast cancer [24]. For early diagnosis of breast
cancer, scientists worldwide have extensively investigated many imaging-based diagnostic methods,
including magnetic resonance imaging [25], positron emission tomography [26], mammography [27] and
contrast-enhanced digital mammography [28]. However, these screening-based methods are expensive
and provide limited image resolution. Although mammography has been considered as the current
standard breast imaging tool, it is less effective for dense breasts and small tumors [29,30]. Recently,
microwave breast imaging has been proposed as an alternative or additional detection method to
mammography for early diagnosis of breast tumor [31]. The microwave breast image quality is affected
by the microwave sensors, the synthetic aperture, and the bandwidth of the probing signal [32]. In fact,
the rapid growth of microwave breast imaging systems requires high-performance broadband sensor
that suitable to detect small tumors with cost-effective, compact and easy-to-use measurement system.
Typical characteristics of microwave sensor to be applied for breast tumor detection are: wide
impedance bandwidth, small size, repeatable and cost-effective fabrication, and ability to efficiently
couple power to the breast. Many efforts are underway to identify new sensor characteristics suitable
to satisfy the challenging requirements of the microwave breast imaging systems. This paper presents
a comprehensive review of the scientific literature of the last decade to provide investigators a valuable
support tool to the microwave biosensors for early diagnosis of breast tumor. The present review
focuses on three major parts: electrical properties of tissue, microwave breast imaging and microwave
sensors. A comparative sensing performance, present challenges, and future prospects of label-free
microwave biosensors also discussed in detail.

2. Electrical Properties of Tissue

The microwave imaging based approaches to detect cancer cells are highly related to the dielectric
properties contrast between the healthy tissue and the malignant tissue [33]. Different water-content
biological tissues have distinct electrical properties [34]. Foster et al. [35] reported a critical review
of human tissues. Up to date, scientists have investigated many types of tissues, including breast
tissue [36], liver [37], lymph nodes [38], skin [39], bone [40], and heart [41]. Some factors have been
reported to explain the difference in electrical properties between healthy and malignant tissues include
water content [42], necrosis and inflammation causing breakdown of the cell membrane [43], sodium
content [44], charging of the cell membrane [44], and change in the dielectric relaxation time [45].

2.1. Dielectric Properties of Breast Tissues

Joines et al. [46] measured various fresh tissues (include colon, kidney, liver, breast, muscle and
lung) and malignant tissues from patients at frequency range of 50~900 MHz. It was found that
the conductivity contrast between malignant tissue and normal breast tissue is 6.4:1 and the relative
permittivity contrast between malignant tissue and healthy breast tissue is 3.8:1. For the same type
of tissue, the dielectric contrast between malignant and normal tissues is greatest for the mammary
gland. Jin et al. [47] reported that the dielectric contrast between healthy breast tissue and malignant
breast tissue appears to be inhomogeneous due to the dielectric property changes.
Gabriel et al. [48–50] extensively measured the dielectric properties of 30 different tissues and
found that the dielectric properties of muscle or malignant tumors (high-water-content) are higher
Sensors 2018, 18, 655 3 of 17

than fat or normal breast tissues (low-water-content) over the entire radio frequency (RF) spectrum
of power frequencies through millimeter waves. Lazebnik et al. [51] studied the dielectric properties
of normal breast tissue and cancerous tissue at frequency range 0.5~20 GHz. Their research findings
illustrated that both dielectric constant and conductivity decrease with the adipose content increase,
and conversely as the percentage of glandular and/or fibro-connective tissue increase, both dielectric
constant and conductivity increase. The dielectric properties of normal breast tissues having a wide
range of values depending on tissue type. Chaudhary et al. [52] measured the relative permittivity and
conductivity of normal and malignant breast tissues at RF and microwave frequencies (up to 3 GHz).
The dielectric contrasts between malignant tissue and normal breast tissue were, 4.7:1 and 5:1, these
results were in good agreement with Joines et al.’s results.
The dielectric properties of malignant tumors at different frequencies have been measured and
investigated by many research groups. The experimental results showed that the relative permittivity
and conductivity of high-water-content tissues are almost the same as muscle at frequencies above
1 GHz, however, the relative permittivity and conductivity of malignant tumors are significantly higher
than a muscle at frequencies below 1 GHz [53]. Swarup et al. [54] studied the dielectric properties
of MCA1 fibrosarcoma mouse tumors at different days after inception. No significant variations of
relative permittivity and conductivity were seen by tumor age. While the larger tumors exhibited
a necrotic interior, they showed little difference in the relative permittivity and conductivity above
0.5 GHz. Surowiec et al. [55] investigated cm-size human breast malignant tissues and adjacent tissues.
The dielectric properties of normal breast tissue increased as malignant tissue. This effect may be
caused by infiltration or vascularization. It could enlarge the microwave scattering cross-section and
thereby aid in the confocal microwave detection of the tumor.

2.2. Modelling of Biological Tissue

The dielectric properties of biological tissues are nonlinear functions of frequency [56]. Therefore,
it is a critical task to choose a suitable working frequency for microwave breast imaging system due
to the attenuation of microwave signal increases with the frequency and increase in the conductivity
resulting in a lower penetration depth. Various numerical models include the most popular Debye and
Cole-Cole models have been developed for modelling the biological tissues [57]. The Debye model is
defined as follows [45]:
εs + ε∞ σ
εr = ε∞ + −j (1)
1 + jωτ ωε 0
where ε ∞ is the permittivity and its value highly relative to the water content of the tissue, ε s is the
static permittivity, τ is the relaxation time. The measurements from Joines et al. and Chaudhary et al.
were extrapolated to higher frequencies using the Debye model.
The Cole-Cole model was developed to represent the complex dielectric constant [58]:

εs − ε∞
ε∗ (ω ) = ε ∞ + (2)
1 + ( jωτ )1−α

where ε∗ is the complex dielectric constant, ε s and ε ∞ are the static and infinite frequency dielectric
constants, ω is the angular frequency and τ is the time constant. The exponent parameter α, which
takes a value between 0 and 1 describes different spectral shapes. When α = 0, the Cole-Cole model
reduces to the Debye model. When α > 0, the relaxation is stretched.
Zastrow et al. [59] applied the empirical relationship between the dielectric parameters and
the moisture content model (developed by Foster and Schwan) to further confirm the Debye model.
For an approximate 10% moisture content, the empirical model is:

εs − 4
ε0r = 1.71 f 1.13 + (3)
1 + ( f /25)2
Sensors 2018, 18, 655 4 of 17

εs − 4
σ = 1.35σ0.1 f 0.13 + 0.00222 f 2 [ ] (4)
1 + ( f /25)2
where f is the frequency, σ0.1 = 0.05 and εs = 8.5 were obtained based on the findings reported by
Foster’s et al.

3. Microwave Breast Imaging

Microwave imaging offers an accurate detection of breast tumors with specific reference to the
shape, size and boundary irregularities [60]. During the past two decades, researchers around the
world have investigated numerous of microwave imaging based approaches with particular focus on
breast cancer detection and brain stroke detection. Microwave imaging approaches can be divided
into two main groups: microwave tomography and radar-based imaging.

3.1. Microwave Tomography

Microwave tomography offers quantitative information on dielectric properties of breast tissues to
identify tumors [61]. Microwave tomography produces a map of permittivity and conductivity through
inversion of those signals. However, the inverse problem takes much time due to the calculation
process is complicated. Also, a nonlinear inverse scattering problem must be solved, and iterative
image reconstruction algorithms are usually required to obtain a solution. In general, these ill-posed
inverse scattering approaches suffer from non-uniqueness and require regularization in order to
achieve convergence to a meaningful solution.
Several research groups have investigated microwave tomography breast imaging based on single
frequency and multi-frequency approaches [62–64]. Among these groups, researchers from Dartmouth
College has studied microwave tomography for breast cancer detection since 1990s, which is one of
the representative research groups. They have developed a microwave imaging algorithm to map
dielectric properties in a 2D lossy mediumin. The same research group has first developed a clinical
prototype for imaging of human breasts. The prototype contains 32-channel data collection system
at frequency range 500 MHz to 3 GHz. Clinical trial studies have shown that cm-size breast tumors
could be identified using the multi-frequency microwave tomography technique [65]. However,
microwave tomography requires heavy computation work that causes long image generate time.
Recently, magnetic nanoparticles and compressive sensing techniques have been used in microwave
tomography to represent as the contrast agent to improve the specificity, sensitivity and accuracy of
the diagnosis of breast cancer [66–68].

3.2. Radar Based Microwave Imaging

Radar based microwave imaging is the main type of the microwave imaging-based approaches,
which maps the internal organ structure by measuring the dielectric properties of the tissues [69]. Radar
based microwave imaging has been proposed as a promising tool for early diagnosis of breast tumor
with the advantages of cost-effective, safety, highly sensitive and specific. Additionally, it is a more
comfortable and safer method compared to microwave tomography. Several experimental measurement
systems were developed to demonstrate the radar-based microwave imaging approaches [70,71],
including confocal microwave imaging (CMI) [72,73], microwave imaging via space time (MIST) [74,75]
and holographic microwave imaging (HMI) [76,77].
A CMI was developed and evaluated for breast tumor detection [70]. The experimental results
showed that the 2D CMI system can detect small tumors (2 mm in diameter) and the 3D CMI system
can identify tumors with medium size (greater than 6 mm in diameter). In order to reduce artifacts and
noises and enhance image, the research group has applied a delay multiply-and-sum method in CMI.
However, the CMI method has not been validated on human subjects due to difficult implementation
system. Recently, another major type of CMI method, namely tissue sensing adaptive radar (TSAR)
imaging was proposed for detecting breast cancer [78]. Clinical trial studies indicated that the TSAR
Sensors 2018, 18, 655 5 of 17

imaging method has the ability to detect breast lesions with correct size (greater than 4 mm in diameter)
and location information. However, the TSAR method has the drawbacks of large reflections from skin
and high-cost hardware system. The research team developed the Bayesian estimator to improve the
image quality [79].
A MIST system that contains an array of 16 horn microwave sensors was developed for
microwave breast imaging application [74], the proposed UWB horn sensor significantly improved the
performance of breast cancer detection. However, artifacts were produced in the reconstructed images
using MIST method. To improve the accuracy of the detection, the same research team has upgraded
the measurement system. The experimental results demonstrated that the upgraded system can detect
small tumors (4 mm in diameter).
Elsdon et al. [80] proposed a near-field HMI for imaging of biological objects. Compared to
other radar-based microwave imaging approaches, HMI has advantages in low-cost due to expensive
ultra-high-speed electronics are not required as narrow-band signals can be converted to the baseband
for digitization at a slower rate. However, the proposed near-field HMI technique only experimentally
tested on a simple phantom. Different from Elsdon’s work, Wang et al. [81] recently developed
a far-field HMI for breast tumor detection. The simulation and experimental results showed that
various arbitrary shaped breast tumors with random sizes and locations can be clearly identified in
the reconstructed breast images using the proposed single frequency HMI technique. The far-filed
HMI method requires long data acquisition time, especially when generating 3D images. To solve this
challenge, the authors recently applied compressive sensing technique in HMI to produce high-solution
image using much less sampling rate. However, further experimental validations on realistic breast
phantoms and human subjects are required in the future.

4. RF Sensors for Biomedical Applications

A radar-based microwave imaging system normally consists of a RF generator to illuminate
microwave signals, RF sensor(s) to transmit microwave signals to the target object and measure the
backscattered reflection signals from the object, and a computer with matched software (contains
microwave imaging algorithm) to analysis the measured data to map the internal structure of the
object. Microwave sensor plays an important role in the microwave breast imaging system. The image
resolution can be improved by applying higher frequencies, develop a high sensitive sensor, and
increase the number of the sensors applied in the system. In addition, smaller sensors enable a more
number of sensors in the sensor array and enhance image resolution [82,83]. Various types of RF
sensors have been developed for biomedical applications, which can be divided into the two main
groups: microwave sensor for implementation of microwave breast imaging systems and microwave
biosensor for cancer biomarkers detection.

4.1. Microwave Sensors for Microwave Breast Imaging Systems

To date, numerous broadband and planar printed monopole microwave antennas have been
developed for breast cancer detection due to their simple structure, broadband property, compact size,
and ease-to-fabricate [84–86]. Recently, few flexible antennas were proposed to apply in the microwave
sensor array for breast tumor detection [87–90]. Among these sensors, microstrip antenna is one of the
most popular types of sensors developed for applying in microwave breast imaging systems because
its compact size, inexpensive and can be printed directly onto a circuit board. A microstrip antenna
normally contains a patch (metal foil) placed on the surface of the top board and a ground plane
on the bottom side of the board, and the patch is normally made in different shapes such as square,
rectangular, circular and elliptical [91].
In 2005, Shannon et al. [92] designed a slot line bow tie microwave antenna for identifying breast
tumor. The antenna was immersed in a dielectric medium and fed with an integrated UWB balun.
Both numerical and experimental validations were conducted to demonstrate the characteristics of the
antenna on breast phantom with various cylindrical tumors. The obtained results showed that return
Sensors 2018, 18, 655 6 of 17

loss of 10 dB is obtained in the frequency range of 2.5~9 GHz, and return loss of 5 dB is obtained in the
frequency range of 1~10 GHz. Breast tumor (7 mm in diameter) at a depth of 4 cm from the aperture
was successfully detected.
In 2007, Nilavalan et al. [93] developed a low-profile stacked-patch antenna to radiate directly
into a breast tissue model at frequency range of 4~9.5 GHz. This antenna produced a bandwidth
◦ ◦
of approximately 77% and beamwidths of approximately ±40o in the φ = 0 plane and ±30 in the
◦
φ = 90 plane at 6.5 GHz. The antenna has been tested on breast phantom and experimental results
showed that the proposed microstrip patch antenna has the potential to be applied in the microwave
breast tumor detection system.
In 2009, Shenouda et al. [94] proposed a dielectric-immersed antenna for a breast tumor detection
system. The antenna had a tapered slot line that operates in a low permittivity dielectric. The sensor
was fed with a microstrip-to-slot line balun at frequencies 2~12 GHz. Various phantoms were placed
in a homogeneous to evaluate the suitability of the antenna for biomedical application. The antenna
and balun were measured in canola oil, and good agreement between simulation and measurement
was obtained. The −10 dB reflection coefficient bandwidth of the balun and antenna was obtained at
frequencies 3~10.6 GHz. However, further validations on a more realistic 3D breast phantom were
required in the future.
In 2010, Bourqui et al. [95] developed a balanced antipodal Vivaldi antenna for applying in the
TSAR system. The antenna made of three copper layers, the two external layers were connected to
the feeding line ground planes and the central layer was connected to the signal conductor of the
feeding line. The experimental results showed that the antenna provides better return loss above
2.4 GHz. The lower limit of the desired frequency bandwidth (2~12 GHz) was not reached, however
the antenna still shows better than −7 dB reflection at that frequency. Gibbins et al. [96] developed
a stacked-patch antenna and a wide-slot antenna for the purpose of breast tumor detection. The size of
the wide-slot antenna was 3 times smaller than the stacked-patch antenna. The experimental results
demonstrated that both antennas had suitable bandwidths for application in the UWB system and
good agreement was found between simulation and experimental results for the wide-slot antenna.
They also developed a hemispherical antenna array made of 16 stacked-patch antennas for breast
tumor detection. Experimental results showed that the hemispherical antenna array can detect 8 mm
spherical breast tumor phantoms at different locations.
In 2011, Wang et al. [97] designed a compact microstrip slot antenna for microwave breast
imaging. The matching solution medium was required for the experimental performance. The antenna
was experimentally validated on breast phantom and experimental results showed that it has
achieved a good matching performance at 2~8 GHz. The antenna has the potential to be applied
in a half-spherical antenna array for breast cancer detection, and it can also be adapted for other
biomedical applications such as knee imaging.
In 2012, Chan et al. [98] designed and optimized a resistively loaded wire bowtie antenna based
on a genetic algorithm approach and some empirical investigations. The antenna was experimentally
tested in free space and within a tissue-like phantom. The impedance bandwidth of 100.75% was
achieved with a VSWR < 2 at a frequency of 3.3~10.0 GHz. The experimental results agreed with
the simulation results and both simulation and experimental results demonstrated that the proposed
design has the potential for applications in microwave breast imaging prototype. In the same year,
John et al. [99] developed an UWB bow tie sensor and a sensor array that made of 12 panels and each
panel made of 3 UWB bow tie sensors for microwave breast imaging application. The coupling medium
was filled in the cavity, and an image of a spherical object was reconstructed by using an inverse
scattering algorithm. Bowtie sensor has benefits in compact, wideband and easy-to-manufacture.
In 2013, Wang et al. [100] developed an open-ended waveguide sensor for application in an
HMI system for detecting breast tumor. The spiral sensor array and random sensor array were
proposed and compared with the regular spaced sensor array. Each sensor array was made of
16 open-ended waveguide sensors with one worked as the transmitter and the others worked as the
Sensors 2018, 18, 655 7 of 17

receivers. The sensors offered good performance in the frequency range of 10~20 GHz. Both simulation
and experimental results demonstrate that the proposed waveguide antenna has the ability to identify
small breast tumors located at breast phantoms. The breast phantom image quality was significantly
improved by using spiral and random sensor arrays.
In 2014, Nepote et al. [101] proposed a horn antenna for breast radar imaging applications in the
frequency range of 1.5~6 GHz. The designed horn antenna was experimentally evaluated on various
breast phantoms and the results were compared with the Vivaldi sensor. Images obtained using the
horn antenna had a lower noise level and higher contrast than the images obtained using the Vivaldi
antenna. In the same year, Ahadi [102] developed a square monopole antenna to identify breast tumor.
Effect of variation in different parts of the antenna was analyzed and presented to optimize the antenna
for its best operation. The design was numerically and experimentally validated to demonstrate its
characteristics. The results showed that the antenna has <10 dB feed match at frequency 4 GHz to
more than 9 GHz. It has been represented that in order to minimize the distortion in the transmitted
signal through the breast the antenna S21 is about 5 dB at a frequency range of 4~8 GHz, which is
suitable for the microwave imaging application.
In 2015, Kahar et al. [103] proposed an UWB microstrip monopole antenna for imaging of
heterogeneous breast model. A heterogeneous breast model was developed to validate the proposed
antenna with different locations from skin and tumor. Simulation results showed that the antenna has
high gain, phase linearity, and good polarization characteristics. High current density was observed in
the most deep-seated tumor as well as for the smallest tumor, keeping SAR values on breast tissues
well within safe limits. The best simulation results were achieved when the antenna was placed at
1 mm away from skin. Bahramiabarghouei et al. [87] developed a single microstrip sensor array and
a dual polarization microstrip sensor array for radar-based imaging application. The sensor arrays
made of 16 flexible monopole antennas and 16 flexible spiral antennas, respectively. The operating
frequency range was 2~4 GHz for both arrays. Experimental results showed that the developed flexible
antennas have good impedance matching when in different positions with different curvature around
the breast. By using a reflector for the arrays, the penetration of the propagated electromagnetic waves
from the antennas into the breast can be improved by factors of 3.3 and 2.6, respectively.
In 2016, Karli et al. [104] developed a compact microstrip antenna for implementation in an UWB
microwave imaging system. The design was numerically and experimentally tested on various breast
phantoms for identifying breast tumors. The experimental results demonstrated that the proposed
antenna has sufficient sensitivity and effectiveness to detect tumors when the antenna is in contact
with the breast skin. Such design may enhance the accurate detection of breast tumors when it is
applied in the imaging measurement system. Li et al. [105] designed a circularly polarized implantable
patch antenna for industrial, scientific, and biomedical applications. The proposed antenna can
obtain improvement for both impedance bandwidth and axial ratio bandwidth, without increasing
the backward radiation. The proposed antenna has the potential for biomedical applications at
2.45 GHz. In the same year, a cost-effective wearable bra was developed for microwave breast cancer
detection [89]. The bra contains an array of 16 flexible microwave sensors, which is highly cost-effective
compared to typical table-based microwave imaging systems. The developed wearable prototype was
tested on healthy volunteers. Experimental results showed that the proposed wearable bra offers better
performance than the table-based microwave imaging system. However, only one healthy volunteer
was involved in this study, further experimental validations on a wider range of human subjects with
varying breast size and density are required in the future.
In 2017, Li et al. [106] applied cost-sensitive ensemble classifiers to the microwave imaging system
(see Figure 1) to identify abnormalities in the breast. A hemispherical ceramic dielectric radome was
designed for performing breast scans on subjects, which houses the target breast and the 16-element
microwave sensor array. A gel (such as ultrasound gel) or liquid was filled in the space between the skin
and the randome walls, due to the fact that the radome was designed for a largest breast size. During
data collection, a Gaussian-modulated pulse wave was generated and shaped by a passive microwave
Sensors 2018, 18, 655 8 of 17

filter in the frequency range of 2~4 GHz. The transmitted and reflected signals from the breast were
measured and recorded by all microwave sensors located in the sensor array. The total of 240 signals
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Sensors 2018, 18, 655 10 of 17

4.2. RF Biosensors for Cancer Biomarker Detection

RF biosensor offers a promising new approach for accurate, safe, label-free, and rapid diagnosis of
biomolecules and cancer cells. Compared to RF sensors, RF biosensor offers low-cost, disposable, and
high-sensitive option for biomolecule diagnostic systems. RF biosensors can be classified as near-field
biosensors and far-field biosensors. The section mainly addresses near-field RF biosensors. Microwave
components, such as transmission lines, lumped capacitors, waveguides, fabricated on a substrate and
used for detection of biological materials, can be termed as passive sensors [108]. The design of RF
biosensor requires to meet the specific design requirements, such as working frequency, bandwidth,
directivity, sensitivity, accuracy, compact size and low cost. Various nanomaterials have been applied
to develop RF biosensors in order to enhance the sensitivity of biomolecule detection.
Lee et al. [109] developed a planar split-ring resonator-based microwave biosensor for label-free
detection of biomolecules such as prostate cancer marker, prostate specific antigen (PSA), and cortisol
stress hormone. The biosensor consisted of a resonance-assisted transducer and was excited by
a time-varying magnetic field component of a local high-impedance microstrip line. The device
exhibits an intrinsic S21 resonance with a quality-factor of 50. For the Biomolecular interaction,
anti-PSA and anticortisol were immobilized on the gold surface of the resonator by a protein-G
mediated bioconjugation process and corresponding frequency shifts of 30 ± 2 MHz (for anti-PSA)
and 20 ± 3 MHz (for anti-cortisol) were observed.
Yang et al. [110] developed a multilayered polymeric DNA biosensor using RF technology with
gold and magnetic nanoparticles to enhance the detection sensitivity of DNA. Previous studies have
shown that the nuclear magnetic resonance-based RF biosensor has an ability to detect various
biomolecules such as avidin, human chorionic gonadotropin, and human bladder cancer cells.
Kim et al. [111] developed a wireless RF biosensor to demonstrate the biomolecular binding systems
such as biotin–streptavidin and DNA hybridization. Chen et al. [31] proposed a microwave biosensor
dedicated to the dielectric spectroscopy of a single and living biological cell in its liquid culture
medium in the micro and millimeter wave ranges. The sensor worked in the near field and involves
a capacitive gap to perform the electromagnetic sensing, while a microfluidic system was developed
and adapted to the RF circuit to precisely localize the single biological cell under study. Both capacitive
and conductive contrasts of a living biological cell measured in its culture medium were accessible.
A living B lymphoma cell was measured in the frequency range of 40 MHz~40 GHz, with a measured
capacitive contrast of the order of several hundreds of attofarads.
Camli et al. [112] designed a simple and cost-effective microwave biosensor based on microstrip
antenna driven ring resonator for label-free detection of glucose. Simulation and experimental
validations were conducted to demonstrate the sensing capacity for changes in dielectric properties of
the surrounding medium. The simulation and experimental results were in good agreement. Recently,
Garrett et al. [113] reported the significant progress made on the average dielectric property analysis
of complex breast tissue with microwave transmission measurements. More recently, Tselev et al. [114]
applied the microwave microscopy for in situ imaging of live biological cells to identify changes in
malignant tissues.

5. Challenges and Future Works

Microwave imaging has been recently proposed as an alternative or additional approach to the
current standard X-ray mammography for early breast cancer detection. Apart from microwave
imaging algorithms, microwave sensors and sensor arrays have been reported play the most important
role in the microwave imaging systems for diagnosis of breast tumors. Some major limitations
have been reported for practical implementation of microwave imaging-based methods, including
low dielectric property contrasts between the healthy and the malignant tissues, working frequency
selection, development of a high sensitivity microwave sensor, and limited image resolution. Previous
studies have suggested that it is necessary to develop a high sensitivity microwave sensor and
a sensor array to improve the image resolution and reduce the system cost. Many investigators have
Sensors 2018, 18, 655 11 of 17

increased the number of implementation sensors in a microwave imaging sensor array to improve
the image quality, for example, Kurrant et al. [115] increased the number of microwave sensors in
the measurement system from 16 to 256. However, this increment may reduce the accuracy of tumor
detection due to the mutual coupling signals caused between sensors. Moreover, the total operating
cost of the system will be increased and the measurement system will be becoming more complex with
increasing the number of sensors.
To address these challenges, investigators recommended that more investigations should be
provided on the development of a high dynamic measurement system with particular focus on
high sensitive, compact and low-cost microwave sensors and sensor arrays to achieve high quality
images. In recent years, many researchers have developed a numerous of high sensitive RF sensors for
application in the microwave imaging system for detecting breast tumors. Most of these sensors have
been extensively tested on various simplified breast phantoms both numerically and experimentally.
Coupling solution medium was filled in the space between the target object and the sensors in most of
microwave imaging systems in order to reduce the noise and improve the image resolution. However,
such method also increases the operating cost significantly. Optimization of sensor arrays such as using
unequally spaced sensor arrays and applying compressed sensing approaches in the signal and image
processing may be other solutions to improve the image quality in a fast and cost-effective manner.
In recent years, biosensors and biomarkers-based techniques for early breast cancer detection
have attacked many people’s interests. To date, cancer biomarker discovery is still in its discovery
stage and the evidence is too restricted to confidently apply biomarkers as diagnostic tools for
diagnosing early-stage breast cancer. Protein biomarkers have utility within a panel of biomarkers,
however, they have not been recommended as individual biomarkers to detect breast cancer. Biosensor
techniques have some important drawbacks that are related to the integration of the diagnosis of breast
cancer in primary health care. For instance, QCM-based biosensors are more common and reliable
platforms than other types of sensors for surgery applications. However, there are some drawbacks of
biosensors such as small target size, marker levels, the possibility of high non-specific binding in the
case of serum or real patient samples. Recent research trends of nano-biosensors and RF biosensors
for biomolecules offer great potential for early cancer detection. However, these techniques are not
mature for clinical trials. Future investigations should be addressed directly to improve the selectivity,
sensitivity, accuracy, and multiplexing capacity of microwave sensors.

6. Conclusions
Successful clinical trials of microwave breast imaging demonstrated that microwave imaging
has the potential to become an additional or alternative method to the current standard X-ray
mammography for detecting breast tumors in their early stages. Microwave sensor plays the most
important role in the microwave imaging measurement systems. This paper presented an exhaustive
summary of microwave sensors for applications in microwave imaging approaches for breast tumor
detection, including electric properties of biological tissues, microwave imaging methods, microwave
sensors and microwave biosensors. Microwave images of breast have direct impacts on spatial
resolution, microwave sensors and sensor arrays, optical choice of frequency, detection accuracy and
quality of imaging. Several advantages of existing microwave sensors, open challenges, possible
solutions and future work directions also discussed.

Acknowledgments: The author gratefully acknowledges the financial supports from the National Natural
Science Foundation of China (Grant No. 61701159), the Natural Science Foundation of Anhui Province (Grant
No. 101413246, JZ2017AKZR0129), the Foundation for Oversea Master Project from Ministry of Education, China
(Grant No. 2160311028), and the start-up funding from the Hefei University of Technology (Grant No. 407037164).
Author Contributions: Lulu Wang designed, conducted the study, and wrote the paper.
Conflicts of Interest: The author declares no conflict of interest.
Sensors 2018, 18, 655 12 of 17

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