Sensors International 1 (2020) 100028

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Sensors International
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Detection of pathogenic bacteria with special emphasis to biosensors

integrated with AuNPs
Neelam Yadav a, b, *, Anil Kumar Chhillar b, Jogender Singh Rana a, **
a
Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, Haryana, 131039, India
b
Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, 124001, India

A R T I C L E I N F O A B S T R A C T

Keywords: Bacteria are unambiguously menacing for community healthiness globally. The common reservoirs of bacteria are
Bacterial infection contaminated foods, animals, polluted water and soil. There are several diseases causing bacteria such as Vibrio,
Nanotechnology Listeria, Yersinia, Salmonella, Shigella, Clostridium, Campylobacter and many more. The apprehension for the
AuNPs
transmission of bacterial infection has increased the incidence of outbreaks and several health issues across
Biosensors
Bacterial infections
boundaries. The key challenge for treatment of bacterial infection in early stage is the investigation of multiplexed
bacterial virulent factors. Therefore, it requisites the development of highly efficient techniques to identify,
prevent and manage growth of pathogenic bacteria for the well-being of living system. Conventional techniques
including serological tests, immuno assays, polymerase chain reaction (PCR) and isothermal microcalorimetry
(IMC) and many other techniques have been used for the testing of bacterial infection. However limitations of
aforesaid techniques have been overcome by biosensing techniques as they have offered numerous advantages
including highly simple, sensitive, specific, cost effective and quick response generating reproducible, on-site
detection and ease of portability. Present review article deciphers the role of distinct types of biosensors based
on gold nanoparticles for the analysis of bacteria from different reservoirs.

1. Introduction intestinal infections, renal disorders, central nervous disorders, arthritis,

Foods are the natural and inevitable reservoirs of microbial popula-
tion [1]. Cooking of foods at high temperature kills the bacterial patho-
gens however; foods processed at mild heat contain huge population of
microbes which causes pathogenicity to human beings [1]. The chief
bacterial reservoirs of food items include meat, dairy and poultry prod-
ucts. These food items have facilitated the growth of several microor-
ganisms like Salmonella, Campylobacter, Listeria, and Escherichia coli
O157:H7 [2]. Therefore, such foodborne pathogens have increased the
risk of pathogenicity. According to an estimate reported by World Health
Organization (WHO) revealed that approximately 93.8 million people
have been susceptible to foodborne diseases and about 155000 people
mortality is due to foodborne pathogens annually [3–5]. The pathogenic
bacteria have caused several health complications such as repetitive
and blindness [6]. Hence, diagnosis of bacterial pathogens has been
carried out by a number of conventional techniques including serological
tests, enzyme-linked immunosorbent assay (ELISA), PCR and IMC [7].
Here we have discussed some of conventional approaches used in diag-
nosis of bacterial infection.
2. Detection of bacterial pathogens by conventional methods
2.1. Nucleic acid (NA) based methods
These techniques detect the particular DNA/RNA segment of infect-
ing bacteria. Zhao et al. [8] have revealed the investigation of targeted
DNA/RNA sequence by hybridizing nucleic acid sequence of specific
bacterial pathogen with the complementary oligonucleotide segments

* Corresponding author. Department of Biotechnology, Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, Haryana, 131039, India.
** Corresponding author. Department of Biotechnology, DCRUST, Murthal, Sonepat, India.
E-mail addresses: neelamindia12@rediffmail.com (N. Yadav), jsrana@outlook.com (J.S. Rana).

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https://doi.org/10.1016/j.sintl.2020.100028
Received 27 April 2020; Received in revised form 18 June 2020; Accepted 19 June 2020
Available online 5 August 2020
2666-3511/© 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-
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N. Yadav et al.
that may be probes or primers. A number of bacteria namely Clostridium
botulinum, Vibrio cholerae, Staphylococcus aureus, and Escherichia coli
(E. coli) O157 have been reported for production of toxins and thereby
cause pathogenicity [9–11]. Thus, these pathogens can be detected by
using nucleic acid based techniques. Different types of PCR like multi-
plexed polymerase chain reaction (mPCR), real time PCR (RT-PCR),
nucleic acid sequence based amplification (NASBA) and loop mediated
isothermal amplification (LAMP) have been used for the investigation of
pathogenic bacteria.
2.1.1. Detection of bacterial pathogens using PCR
PCR is widely used technique to analyse the samples with bacterial
pathogen. Velusamy et al. [12] have reported that PCR can detect single
bacteria by identifying NA sequence of target bacterial pathogen. In this
technique firstly bacterial NA sequence is converted into single stranded
from double stranded. After that specific oligonucleotide segment i.e.
primer binds complementary with the bacterial single stranded NA
sequence. The NA sequence of L. monocytogenes, E. coli O157:H7,
S. aureus, Campylobacter jejuni, Salmonella spp. and Shigella spp have been
detected by PCR [13–15].
2.1.2. Detection of bacterial pathogens using mPCR
This type of PCR involves multiple primers to amplify target DNA
sequence. The basic mechanism of amplification is similar to the simple
PCR [8]. Furthermore primers designing and their concentration used
during PCR reaction are very important parameters because very high
primers concentration may increase the interaction between the multiple
oligonucleotides. mPCR has been used for the investigation of S. enteritidis,
S. aureus, S. flexneri, L. monocytogenes, and E. coli O157:H7 [16]. Beside this,
Ryu et al. [17] have demonstrated the use of mPCR for the analysis of
Listeria species namely L. monocytogenes, L. grayi, L. ivanovii, L. innocua, L.
welshimeri, and L. seeligeri [17]. They reported 7.58
104 copies detection
limit for mixed NA sequence of Listeria species.
Earlier mPCR had been employed for the investigation of only two or
three microbes. Currently, this technique has been used for simultaneous
detection of more than five microorganisms. The advancement of mPCR
led to invention of another new technique that is GeXP-PCR [18]. This
GeXP-PCR was used to detect six bacteria viz. Salmonella enterica, Listeria
monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, Shigella
spp. and Campylobacter jejuni. The genome analysis by GeXP can detect
several bacteria in only one reaction.
2.1.3. Detection of bacterial pathogens using qPCR
In this type of PCR, the amplifying sequence can be visualized
simultaneously during PCR reaction. The quantity of amplified PCR
product has been measured by monitoring fluorescence signals that de-
pends on concentration of PCR product [19]. The working of qPCR de-
pends on fluorescent systems. There are three main fluorescent systems
for qPCR include SYBR green, TaqMan probes and molecular beacons. It
has been observed that low intensity fluorescence was emitted when
SYBR green intercalate non-specifically to major groove of
double-stranded DNA (dsDNA) [20]. Therefore, the intensity of fluores-
cence can be enhanced by binding of fluorescent dye in minor groove of
the DNA [21]. The other fluorescent system is TaqMan probes that are
double stranded oligonucleotides consisting fluorescence emitting re-
porter dye at the 50 end and quencher dye at 3'end [20]. These dyes are in
near vicinity to one another to inhibit the fluorescence emitted by re-
porter [22]. Molecular beacons are oligonucleotide probes comprising
sequence corresponding to specific segment and binding of this sequence
emit fluorescence [23]. This type of PCR has been used for the investi-
gation of Salmonella, Vibrio parahaemolyticus and S. aureus [24]. The
detection limits for these bacteria were 4 CFU/25 g, 102 CFU/mL and
1
104 CFU/mL respectively [24].
2.1.4. Detection of bacterial pathogens using LAMP
This approach was firstly employed by Notomi et al. [25] to analyse
target bacteria. The working of this technique involves auto cycling to
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Sensors International 1 (2020) 100028
displace DNA stand during synthesis of DNA using Bst DNA polymerase at
high temperature (59–65  C). The time duration to complete one cycle is
60minutes. In LAMP, total 4 primers are used for the amplification of six
precise sites of target DNA. Law et al. reported the investigation of stxA2
gene in E. coli O157:H7 [24]. The specificity of this technique was due to
use of four distinct primers to target six different segments and conse-
quently has provided fast multiplication, and low limit of detection than
PCR approach [26]. Mori and Notomi [25], have reported the bacterial
infection caused by distinct bacteria including Listeria, Salmonella,
Campylobacter, Legionella, and E. coli can be accessed by using commer-
cially available bacterial diagnostic kits [25].
2.1.5. Detection of bacterial pathogens using NASBA
This method is commonly used to amplify target RNA segment by
recruiting enzymatic machinery that comprises reverse transcriptase, T7
RNA polymerase and RNaseH and avian myeloblastosis virus (AMV) [8].
Law et al. [24] have used the application of NASBA for the detection of
several bacteria like S. enterica, V. cholerae, S. aureus, Campylobacter
jejuni, and Campylobacter coli. Nadal et al. have reported 400 CFU/mL
detection limit for the L. monocytogenes [27]. The reaction temperature of
this technique was approximately 41  C [8]. The products obtained from
post-NASBA were detected by agarose gel electrophoresis ELISA. How-
ever, these approaches were complicated, and expensive. Consequently,
Researchers developed an advanced approach of NASBA that is real-time
NASBA (RT-NASBA). This RT-NASBA requires oligonucleotides as a
probe (molecular beacons) that was fluorescently labelled probes as a
result generated homogenous NASBA test [8]. Moreover, RT-NASBA has
been used for the differentiation of viable cells from non-viable cells by
detecting the RNA of target cells and degraded the mRNA of scarified
cells through RNase activity [28].
2.1.5.1. Disadvantages of NA based techniques. Though aforesaid NA
techniques were used for the sensitive detection of bacteria but these
techniques exhibited a number of limitations such as complex procedure,
expensive, less reliable, need large quantity of sample and lengthy
procedure.
2.2. Detection of bacterial pathogens using culture based approaches
Identification of target infectious bacteria has also been monitored
through culture based approaches. For illustration MacConkey agar
(SMAC) was used for the investigation of E. coli O157:H7 [29].
Furthermore, Tan et al. detected Y. enterocolitica and non Y. enterocolitica
on Cefsulodin-Irgasan-Novobiocin (CIN) agar media [30].
2.2.1. Disadvantages of culture based approaches
The major disadvantages of culture based approaches are more time
consuming due to slow growth of bacterial cells, less reliable as they
sometimes give pseudo results and thus less sensitive and specific [31].
2.3. Detection of bacterial pathogens using ELISA
Detection of bacteria in the samples can be analysed by ELISA are
based antigen and antibody (Ab) interaction [24]. In these immunolog-
ical assays primary Abs were confined on microtitre well plate followed
by the binding of target bacteria to primary Abs. after that secondary Abs
bind with enzymes were bind to Ag. This binding produces coloured
signals that can be easily detected. ELISA has been reported for the
investigation of bacteria like Vibrio parahaemolyticus [32] and Salmonella
[33]. The detection limits of these bacteria were 103 cells and 1CFU/25 g
sample. Earlier reports suggest that sandwich ELISA can be employed for
the investigation of a number of microorganisms responsible for causing
foodborne disorders. Furthermore, ELISA test kit for instance BIOLINE
Salmonella ELISA Test was used for the evaluation of Salmonella in food
samples. The detection limit of this test kit was1CFU/25g sample with
N. Yadav et al.
Fig. 1. Diagrammatic depiction of working and principle of a biosensor.
minimum four of the 20 food matrixes tested [33]. It has been reported
that the bacterial toxins of C. perfringens α, β, and ε, s. enteroxins A, B, C,
and E, botulinum toxins and E. coli enterotoxins had been detected by
ELISA [8].
2.3.1. Disadvantages of ELISA
These immunoassays are time consuming, less sensitive and Abs are
prone to degradation.
However, these conventional approaches have several setbacks
including time-consuming, costly and need of highly trained person for
their operation. Therefore, it is necessary to find better alternatives to
existing technologies that should be simple fast analysis of bacteria [34].
Recently, scientific communities have shown their interest for
nano-approaches by synthesizing nanoparticles. As these nanoparticles
have exhibited unique characteristics like small size, electronic, distance
dependent colorimetric alterations and help in surface functionalization;
and therefore employed in diverse sensing devices [35]. Consequently,
they have been used to resolve the issues of conventional diagnostic and
therapeutic system [36,37]. In this review article we have described the
characteristics features of gold (Au) nanoparticles (NPs) and their ap-
plications in biosensing technology.
3. Properties of gold nanoparticles (AuNPs)
AuNPs have been widely used in research applications due to their
flexibility in dimension as well as in configurations such as spherical,
diamond, crystalline, triangular and spiral shapes [38,39]. Due to
nanosize dimension, AuNPs have exhibited unique properties of physical,
chemical like electrical, catalytical, optical and magnetic in comparison
to native Au. Consequently, AuNPs have been found more stable, resis-
tant at high temperature and can absorb and emit light just because of
their optical properties [40]. It has been reported that AuNPs have also
been used in impurity control for example air purification and respiratory
masks [40]. These AuNPs can bind with physiological components
including peptides, proteins, DNA and biochemical polymers, complexes
and fusion materials that have been used in diverse medical applications
[41]. AuNPs ranges from 10 to 100 nm are suitable for medical pro-
spective while size larger than 10 nm are passed out via kidney and size
above 200 nm can be removed through body's immune system [42–44].
Furthermore, AuNPs have shown best optical absorbance and their
absorbance spectra can be fixed at precise wavelength in the near
infrared region. Biosensing devices integrated with AuNPs have not
shown any harmful effect to living organism and help in fast detection of
diseases causing microbes [45].
Applications of AuNPs have been reported in preparation of nano-
medicines [46]. In the last fifty years, several reliable, reproducible and
high yielding methods for their preparation have been developed [47].
AuNPs have shown dimension dependent several fascinating properties
and use of their minute concentration [48]. AuNPs have exhibited unique
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Sensors International 1 (2020) 100028
features in Surface Plasmon Resonance (SPR) phenomenon as they have
shown extraordinary absorption ability and reflecting cross sections. It
has been reported that AuNPs can be easily modified with immuno-
globulins, DNA/RNA probes, glycoproteins [48,49]. Nanoparticles have
been designed from Ag, ZnO, Co and many more, however these NPs
have imparted toxicity to living cells their by restrict their use in in vivo
applications [50,51]. Therefore, composite NPs have gained much more
attention in pharmaceutical applications. For instance, super-
paramagnetic gold nanoshells have exhibited wide application applica-
tions in diagnostics, therapeutics, imaging and biosensing [52,53].
International Organization for Standardization (ISO) guidelines, the size
dimension of NPs ranges between 1 and 100 nm [50,54]. Due to various
favourable properties of AuNPs, they have been used in investigation of
bacteria. For instance, bacteria namely Salmonella spp, Helicobacter pylori
DNA and Mycobacterium tuberculosis have been detected colorimetrically
using AuNPs [55,56]. Furthermore, biosensing devices based on modi-
fied AuNPs have analysed the bacteria by reducing their incubation time
[57]. Use of biosensor technology has aroused the interest of scientists
because of their miniaturization, high specificity, sensitivity, ease in
transportation and automation [58], furthermore, requirement of small
amount of sample and reagent that make their use cost-effective [59].
Moreover, AuNPs based biosensors have also been developed for the
on-site detection of analytes. For instance Fu et al. [60] have constructed
lateral flow biosensor for the in-field evaluation of brochilator compound
known as clenbuterol used as an antagonist for pulmonary diseases and
ingestion of this compound causes cardiac problems. Bu et al. [61] have
revealed the onsite detection of foodborne bacteria S. enteritidis. More-
over, Jiang et al. [62] reported the in-field investigation of E. coli
O157:H7 in the real samples.
Researchers have developed AuNPs based biosensors for the investi-
gation deadly diseases causing microorganisms [63]. It has been docu-
mented that AuNPs integrated biosensors have been fabricated for the
investigation of microbial DNA sequences [64], proteins [65], enzymes
[66], and pathogens [67]. AuNPs have been used for the designing of
biosensing devices as they are easily soluble in water, and facile synthesis
procedures, compatibility in configuration, and also provide active site
due to surface functionalization [68]. Hence, biosensors have been found
suitable for the scrutinization of infectious bacteria [69]. For instance,
electrochemical nucleic acid biosensors have been reported for the
investigation of bacteria/viruses found in contaminations of medical,
pharmaceutical and environment [70].
4. Working and principle of biosensor
A biosensor is a self-contained quantitative analytical approach that
consists of biorecognition and transducing element. Significant signal
generated after interaction of analytes and biorecognition element is
detected by transducing component [71,72]. Biosensors are of different
types depending on type of transducing components used [73,74]. The
N. Yadav et al.
various types of biosensors include piezoelectric, optical, thermal, elec-
trical, amperometric and potentiometric biosensors. Schematic repre-
sentation of working and principal of a biosensor has been depicted in
Fig. 1. Qiao et al. [6] have reported that complex of antimicrobial pep-
tides and AuNPs based electrochemical, optical and piezoelectric bio-
sensors have played a significant application to investigate several types
of foodborne pathogens.
4.1. Classification of biosensors
On the basis of different types of transducers used, biosensors are of
following different types:
4.1.1. Optical biosensors
These optical sensors employed for effective detection of foodborne
microorganisms [75]. The transducers used in such devices measure the
analytical signals in the form of absorbance, fluorescence and reflectance.
Surface Plasmon Resonance (SPR) has been found most effective optical
biosensing approach as it can investigate specific, rates of bacterial
infection detection and possible molecular interactions [76].
4.1.1.1. Investigation of bacterial pathogens by means of optical bio-
sensors. Corripio et al. [1] have detected the Salmonella bacteria by
fabricating optical biosensor integrated with fluorescently conjugated
Staphylococcal protein A at the surface of AuNPs which was further
modified by using immunoglobulins labelled with fluorescein isothio-
cyanate. The limit of detection of this biosensor was 103 and CFU/mL
and 1 h response time. Moreover, Salmonella spp. was detected by con-
structing optical biosensor using AuNPs [77]. The sensitivity of this
biosensor was <10 CFU/mL, response time less than 9 h, simple,
cost-effective and unique stability. Bu et al. [61] have reported the sen-
sitive detection of S. enteritidis and E. coli O157 in water, lettuce and pork
samples. They investigated these two bacteria by developing AuNPs
based lateral flow strip. The detection limit of this sensor was about
103 CFU/mL, sensitivity 104 CFU/mL and response time 10–15minutes.
Park et al. demonstrated the investigation of Salmonella typhimurium by
optical ELISA [78].
4.1.2. Piezoelectric biosensors
Piezoelectric biosensors measure the altered potential (voltage) of a
material which is exposed to mechanical strain. In these piezoelectric
biosensors, under the influence of an electrical field piezoelectric crystals
vibrate at a specific frequency to produce electrical signal. Quartz Crystal
Microbalances (QCM) can sensitively detect small amounts of analytes in
the samples. Detection principal by these sensors involves the binding of
a piezoelectric sensor with a ligand like specific antibodies and followed
by its dipping into a sample solution containing bacteria. The binding of
any bacteria to the sensor ligand will increases the crystal mass followed
Table 1
Comparison of AuNPs integrated biosensors with highly efficient diagnostic techniques.
Name of detection method Target microorganisms
PCR mPCR Listeria spp.
q-PCR S. enterica
L. monocytes
LAMP Salmoneela spp. and Shigella spp.
NASBA E.coli, L. monocytes
ELISA Salmonella
Optical biosensors integrated with AuNPs S.entericus, E. coli O157
Piezoelectric biosensors integrated with E.coli O157:H7, V. parahaemolyticus, Salmonella spp., S. aureus, L. monocytogenes,
AuNPs Shigella
Colorimetric biosensors integrated with Shigella fexineri
AuNPs
Electrochemical biosensors integrated with E. coli O157:H7
AuNPs
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by proportionate decline in frequency of oscillation. These analytical
devices have been used for the investigation of several bacteria in various
food systems [79].
4.1.2.1. Investigation of bacterial pathogens by means of piezoelectric bio-
sensors. Zheng et al. [80] designed piezoresistant biosensor based on
AuNPs. This biosensor was used for the investigation of pathogenic
bacteria viz. E. coli O157:H7, V. parahaemolyticus, Salmonella spp.,
S. aureus, L. monocytogenes and Shigella in foods, environment and clinical
samples. The response time of biosensor was 1 h with a limit of detection
1–9 cells/mL. Kaewphinit et al. [81] have reported the detection of
Mycobacterium tuberculosis using quartz crystal mass immobilized with
specific DNA probe for bacteria and AuNPs. The detection limit of this
biosensor was 5 pg and exhibited 100% sensitivity. This aforesaid
biosensor revealed the sensitive, specific and cost-effective detection of
M. tuberculosis. Furthermore, E. coli O157 was investigated by fabricating
piezoelectric biosensor [62]. They developed the biosensor by inte-
grating the Au electrode with AuNPs and single stranded DNA probe.
Modified Au electrode was bound to target DNA sequence of E. coli
O157:H7 and their by helped in fast, facile, sensitive and specific
detection of bacteria. The above said piezoelectric biosensor exhibited
2.0
103 CFU/mL detection limit. Guo et al. [82] demonstrated the
development of piezoelectric immunosensor for the detection of E. coli
O157:H7. They fabricate the biosensor by using quartz crystal micro-
balance immobilized with functionalized antibodies and AuNPs. They
reported the detection limit in the range of 0–1 log CFU/mL and 24 h
response time. This biosensor was found effective, specific and quick
detection of E. coli O157:H7 in food samples. One more study was
documented by Chen et al. [83] for the investigation of E. coli O157:H7.
They fabricated AuNPs integrated circulating-flow piezoelectric
biosensor. For this investigation they used two probes; among them one
was specific for the target DNA segment of E. coli O157:H7 while other
was bound with target bacterial DNA sequence and AuNPs that acted as
mass enhancer. The detection limit showed by this biosensor was
1.2
102 CFU/mL and working range between 102 to 106 CFU/mL [83].
4.1.3. Colorimetric biosensors
Colorimetric biosensors have been employed for measuring the
quantity of coloured compounds in the evaluating sample. Investigation
of any analyte in the sample involves the detection of visual analytical
signal in the form of altering the colour of an analyte in the real sample
and then analyse with the colour of standard compound [84]. Detection
of analyte by these biosensors is simple, economic and need not required
highly skilled person for the assessment of sample [85].
4.1.3.1. Investigation of bacterial pathogens by means of colorimetric bio-
sensors. Bu and co-workers [61] fabricated colorimetric biosensor to
investigate S. enteritidis by designing lateral flow strip integrated with
Limit of Response time Reference
detection
7.58
104 – [19]
copies
18.6 fg/PCR 10 h [90]
5 CFU/25 g <30 h [91]
5 CFU/10 mL <20 h [92]
40 CFU/mL 4h [93]
1 CFU/25 g – [33]
103 CFU/mL 10–15minutes [61]
1-9 cells/mL 1h [80]
80 CFU/mL 20minutes [35]
101CFU/mL 45minutes [94]
N. Yadav et al. Sensors International 1 (2020) 100028

Table 2
Assessment of different types of biosensor in terms of distinct analytical parameters.
Name of biosensor Electrode Limit of detection Name of microorganism Detection sample Response Name of nanomaterials Reference
used (LOD) used time

Electrochemical Pencil 30 CFU/mL Escherichia coli O157:H7 – – AuNPs [102]

(Immunosensor) graphite
electrode
Electrochemical Screen 3–9 pM Mycoplasma pneumoniae, – 30minutes AuNPs [103]
(Genosensor) printed Chlamydophila
electrode pneumoniae, Legionella
pneumophila, and
Streptococcus pneumonia
Electrochemical glassy 0.03 mM Mycobacterium tuberculosis Real samples 15minutes gold nanoparticles on the [104]
carbon and Neisseria meningitidis electropolymerized layer of
electrode poly-melamine
DNA electrochemical ITO 1.25 ng/mL Mycobacterium tuberculosis clinical sputum sample – AuNPs [105]
biosensor
Electrochemical Glassy 10.0 cfu/mL Bacillus cereus Contaminated milk 15minutes AuNPs and chitosan [106]
(Immunosensor) carbon
electrode
1
Optical (Genosensor) – 83.3 pg μL Enterococcus faecalis Detection in clinical 17minutes AuNPs [107]
samples
Electrochemical Screen 1.95
102 CFU/ Salmonella pullorum and Food products 30minutes AuNPs [65]
(Enzyme printed mL Salmonella gallinarum including eggs, chicken
immunosensor) electrode meats, chicken heart,
chicken liver, chicken
intestine
Colorimetric biosensor – 100 CFU/mL & Escherichia coli and – 1h Graphene oxide [108]
200 CFU/mL Staphylococcus aureus
Colorimetric – 1 nm mecA gene sequence of – 45 s Graphene quantum dots [109]
(Fluorescence Staphylococcus aureus (GQDs) and gold
resonance energy nanoparticles (AuNPs)
transfer (FRET)
biosensor)
Colorimetric biosensor – – E.coli O157:H7 Yellow corn samples – AuNPs [110]
Electrochemical bi- Screen- – Vibrio cholerae and Vibrio – 300s D-amino acid oxidase [111]
enzymatic biosensor printed parahaemolyticus (DAAO) and Horseradish
carbon peroxidase (HRP) enzymes
electrodes onto a MWCNTs and AuNPs
Electrochemical Glassy 3 CFU/mL Salmonella Pork samples 35minutes GO and AuNPs [89]
(Aptamer-based) carbon
electrode
impedimetric Modified Au 48 CFU/mL E. coli O157:H7 – – Self-assembled AuNPs [112]
biosensor electrodes
Colorimetric – 104 bacteria per Salmonella typhimurium – 15 min AuNPs [113]
mL
Electrochemical Glassy 0.028 nM Xanthomonas citri In real samples – AuNPs [114]
(Immunosensor) carbon
electrode

AuNPs in the drinking water, lettuce and pork samples. This biosensor
has exhibited 103CFU/mL low limit of detection. Colorimetric detection
of Staphyloccocus aureus has been reported by using probes integrated
with AuNPs [86]. They have reported the easy, fast, sensitive, specific
and cost effective investigation of S. aureus in food and clinical samples.
They reported 8.73 ng μL1 detection limit of S. aureus within
10–15minutes. Niu et al. [87] have demonstrated the fabrication of
colorimetric biosensor based on AuNPs for the analysis of Klebsiella
pneumoniae which causes nosocomial infection. They detected the
aforesaid bacteria sensitively and specifically in clinical samples. This
biosensor exhibited 10 fg detection limit and 25minutes response time.
Lateral flow biosensor (LFB) was fabricated by Wang et al. [88]. This LFB
was based on AuNPs for the detection of marine sea foodborne bacteria
namely V. parahaemolyticus. They investigated the abovesaid pathogen in
clinical, food and environmental samples. This LFB has exhibited 10 fg
detection limit with 65minutes response time. Furthermore, Feng et al.
[35] have demonstrated the detection of food borne pathogenic bacteria
namely Shigella flexneri by fabricating aptasensor integrated with AuNPs.
This colorimetric aptasensor was sensitive, specific and produces fast
response i.e. 20minutes. The aforesaid sensor has shown advantages like
simple, effective and ease of on-site bacterial detection. The above said
aptasensor has shown 80 CFU/mL detection limit and a wide working
range i.e. 102 -106 CFU/mL. One more LFB has been designed using
AuNPs for the detection of Pseudomonas aeruginos [8]. This LFB exhibited
10 fg and 40minutes detection limit and response time respectively. Ma
et al. [89] have reported the analysis of Salmonella typhimurium in pork
samples by using AuNPs based surface enhanced raman scattering
aptasensor. This aptasensor has shown 5 CFU/mL detection limit and
10–107CFU/mL. Comparison of various diagnostic techniques has been
depicted in Table 1.
4.1.4. Electrochemical biosensors
The transducers used in these devices measure the electrochemical
signal either in current or voltage [72,73]. The principal of measurement
of these biosensing devices involves the specific chemical interaction
between recognition element and binding analyte in the electrochemical
reaction system [74]. Depending on the type of electrochemical signals
produced, electrochemical biosensors have been classified into potenti-
ometric, amperometric, conductometric, impedimetric systems of anal-
ysis [95]. Amperometric biosensors measure current peaks due to
electrons flow during oxidation reduction reactions of working electrode
[96]. In addition to these amperometric biosensors, potentiometric bio-
sensors can assess the potential/voltage on functional electrode in com-
parison to the auxiliary electrode [97]. Conductometric and
impedimetric devices during electrochemical reactions measure the
altered conductance of analytical solution or impedance of an

5
N. Yadav et al.
Fig. 2. Diagrammatic depiction of challenges associated with AuNPs in clinical applications.
immobilized material. Principally the conductance or impedance of
immobilized layer can be measured by using intermittent electric field
and thus assessing the resultant impedance magnitude for calculating the
system resistance [98].
4.1.4.1. Investigation of bacterial pathogens by means of electrochemical
biosensors. Electrochemical investigation of E. coli O157:H7 has been
carried out by Wang and Alocilja [94], using AuNPs complexed with
monoclonal antibodies which further conjugated with magnetic nano-
particles. This amperometric immunosensor exhibited 101CFU/mL limit
of detection and 45minutes response time. Shoaie and co-workers [34]
constructed an amperometric biosensor using screen printed electrode
that was modified by immobilizing polyaniline and AuNPs. The signifi-
cance of this biosensor was to monitor E. coli in urine and contaminated
water samples having 4 CFU detection limit.
Hajihosseini and co-workers [99] have revealed the differential pulse
voltammetry detection of Helicobacter pylori. They investigated the bac-
teria confining graphene oxide and AuNPs onto glassy carbon electrode.
They obtained 27.0 pM limit of detection and linear range was 60–600
pM. Oliveira et al. [100] have impedimetrically detected the bacteria
namely E. coli, Serratia marcescens, Salmonella enterica and Klebsiella
pneumonia by identifying lipo polysaccharide (LPS). They used Au elec-
trode that was immobilized with CramoLL lectin on the PVM (poly (vinyl
chloride-vinylacetate maleic acid))–AuNpCy (L-cysteine-AuNPs). This
impedimetric biosensor detected abovesaid bacteria within 20minutes.
Zhu and co-workers [101] have constructed an electrochemical impedi-
metric immunosensor using AuNPs. They investigated Clostridium difficile
toxin A and B and obtained 0.61pg/mL and 0.60 pg/mL limit of detection
respectively.
Guner and co-workers [102] have fabricated an amperometric
immunosensor for the detection of E. coli O157:H7. This immunosensor
was fabricated by functionalizing pencil graphite electrode with AuNPs,
multiwalled carbon nanotubes and polypyrrole. The immunosensor
exhibited detection limit 30 cfu/mL and wide linear range
3
101-3x107 CFU/mL. Paredes et al. [103] have designed genosensor
based on AuNPs immobilized onto screen printed electrode for the
investigation of Mycoplasma pneumoniae, Legionella pneumophila, Chla-
mydophila pneumoniae and Streptococcus pneumonia. The detection limit of
this genosensor for above said bacteria were 3 pM, 5 pM, 8 pM and 9 pM
respectively. The comparison between different types of biosensors with
6
Sensors International 1 (2020) 100028
their characteristic analytical parameters has been shown in Table 2.
4.1.4.2. Existing challenges associated with gold nanoparticles and their
solutions. Though, AuNPs have shown several unique characteristics that
revealed their numerous clinical applications [115]. However, there are
several challenges that necessitate the researchers to think before using
their applications for well-being of human beings. The significant issues
of AuNPs integrated tools and devices include reproducibility, reliability,
stability and scalability during preparation [116]. In addition to these,
AuNPs with specific dimensions and shapes can be prepared by using
physical, chemical and biological methods. Physical methods of AuNPs
preparation include microwave and ultraviolet irradiation and laser
ablation that have been found harmful. On the other hand, chemically
AuNPs has been synthesis involves specific chemicals and solvents
however; these chemical have caused several hazardous effects on living
system. Beside chemicals they also need treacherous pH and temperature
that are not ideal [116,117]. Dimension of AuNPs has also greatly varied
with distinct clinical applications. AuNPs have shown problems of
species-specific differences with respect to transmission, pathophysio-
logic response, recognized as foreign by the man immune system and
retention time [116,117]. Fig. 2 depicts the challenges associated with
AuNPs in clinical applications.
Therefore in view of aforesaid issues, researchers have resolved
certain issues like toxicity of AuNPs can be reduced by synthesizing
nanoparticles from biological origins as biological methods are eco-
friendly in nature (Singh et al., 2018) [116,117]. Secondly, internaliza-
tion of AuNPs can be inhibited by the process of PEGylation (Singh et al.,
2018) [116,117]. By this process AuNPs are layered with poly-
ethyleneglycol that enhances the retention time of AuNPs in the circu-
lation. Furthermore, future clinical research will help in better
understanding of the interactions of AuNPs with physiological compo-
nents and hence certainly overcome the above said challenges.
5. Conclusion
There are global serious concerns of human health from attack of
bacterial pathogens. Use of conventional techniques for detection of
bacteria have some limitations like time taking, tedious, costly, need of
trained personnel, less reliable and reproducible. Hence, in this article we
have reviewed distinct types of AuNPs biosensors for detection of
N. Yadav et al.
bacterial pathogens. Due to fascinating properties of AuNPs, they have
been used in several clinical applications. Earlier reported publications
suggest the significant applications of AuNPs based electrochemical
biosensors. These electrochemical biosensors have been found more
effective for the detection of pathogenic bacteria and also showed several
other benefits including economic, highly sensitive, specific rapid and
ease of miniaturization. Moreover, optical biosensors have been used for
the on-site detection of bacterial pathogen. In spite of having a number of
developed biosensors for detection of food-borne pathogens, it is still a
challenge for researchers to fabricate biosensors for the reliable and
effective determination of microorganisms in real food samples.
Declaration of competing interest
There is no conflict among authors of this paper.
Acknowledgement
Dr. Neelam thankfully acknowledges the UGC-Dr. D. S. Kothari Post-
Doctoral Fellowship (Reference id No. F.4-2/2006 (BSR)/BL/18-19/
0107) for providing financial assistance.
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