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Microfluidic Devices for Heavy Metal Ions Detection: A Review

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The contamination of air, water and soil by heavy metal ions is one of the most serious problems plaguing the environment. These metal ions are characterized by a low biodegradability and high chemical stability and can affect humans and animals, causing severe diseases. In addition to the typical analysis methods, i.e., liquid chromatography (LC) or spectrometric methods (i.e., atomic absorption spectroscopy, AAS), there is a need for the development of inexpensive, easy-to-use, sensitive and portable devices for the detection of heavy metal ions at the point of interest. To this direction, microfluidic and lab-on-chip (LOC) devices fabricated with novel materials and scalable microfabrication methods have been proposed as a promising approach to realize such systems. This review focuses on the recent advances of such devices used for the detection of the most important toxic metal ions, namely, lead (Pb), mercury (Hg), arsenic (As), cadmium (Cd) and chromium (Cr) ions. Particular emphasis is given to the materials, the fabrication methods and the detection methods proposed for the realization of such devices in order to provide a complete overview of the existing technology advances as well as the limitations and the challenges that should be addressed in order to improve the commercial uptake of microfluidic and LOC devices in environmental monitoring applications.
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Citation: Filippidou, M.-K.;
Chatzandroulis, S. Microfluidic
Devices for Heavy Metal Ions
Detection: A Review. Micromachines
2023,14, 1520. https://doi.org/
10.3390/mi14081520
Academic Editors: Nam-Trung
Nguyen and Xiujun Li
Received: 2 July 2023
Revised: 20 July 2023
Accepted: 27 July 2023
Published: 28 July 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
micromachines
Review
Microfluidic Devices for Heavy Metal Ions Detection: A Review
Myrto-Kyriaki Filippidou and Stavros Chatzandroulis *
Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 15341 Aghia Paraskevi, Greece;
m.filippidou@inn.demokritos.gr
*Correspondence: s.chatzandroulis@inn.demokritos.gr
Abstract:
The contamination of air, water and soil by heavy metal ions is one of the most serious
problems plaguing the environment. These metal ions are characterized by a low biodegradability
and high chemical stability and can affect humans and animals, causing severe diseases. In addition
to the typical analysis methods, i.e., liquid chromatography (LC) or spectrometric methods (i.e.,
atomic absorption spectroscopy, AAS), there is a need for the development of inexpensive, easy-
to-use, sensitive and portable devices for the detection of heavy metal ions at the point of interest.
To this direction, microfluidic and lab-on-chip (LOC) devices fabricated with novel materials and
scalable microfabrication methods have been proposed as a promising approach to realize such
systems. This review focuses on the recent advances of such devices used for the detection of the
most important toxic metal ions, namely, lead (Pb), mercury (Hg), arsenic (As), cadmium (Cd) and
chromium (Cr) ions. Particular emphasis is given to the materials, the fabrication methods and
the detection methods proposed for the realization of such devices in order to provide a complete
overview of the existing technology advances as well as the limitations and the challenges that
should be addressed in order to improve the commercial uptake of microfluidic and LOC devices in
environmental monitoring applications.
Keywords: microfluidic devices; lab on chip; heavy metal ions; biosensors; water safety
1. Introduction
The environment and human health are threatened by heavy metal ions, such as lead
(Pb), mercury (Hg), arsenic (As), cadmium (Cd) and chromium (Cr), which are present
in water, air and soil. Heavy metals ions can be categorized into those required by living
organisms in small amounts (e.g., iron, manganese, zinc and copper), which only cause
toxic effects in high concentrations, and those (e.g., lead, mercury and cadmium) that are
highly toxic even in small amounts [15].
These contaminants are entering the aquatic and food chains of humans and animals
through both human-related activities and natural phenomena. Some examples that result
in the release of heavy metal ions include industry activities, urbanization, mining and
metals discharges from natural resources, volcanic activities, soil erosion, rainwater and
other physical phenomena [2,3,5,6].
Water is the main element of many processes realized in our every-day life; it is
related to food and beverages, personal and facilities hygiene, and animal and human
healthcare. According to the CDC, heavy metals like arsenic and lead, among others, can
easily contaminate tap water [
7
]. This class of pollutants is characterized by a high toxicity
and a density that is greater than 5 g/cm
3
(five times higher than water density) and also
exhibits a low biodegradability and high chemical stability, resulting in the pollutants
staying present in the environment for a long time. Such heavy metals are detrimental for
fauna and flora, catastrophic to animal and plant habitats and can eventually be lethal to
living organisms, including humans [8,9].
The ways through which heavy metals accumulate into the human body vary and
include inhalation from the atmosphere, the ingestion of contaminated food, the drinking
Micromachines 2023,14, 1520. https://doi.org/10.3390/mi14081520 https://www.mdpi.com/journal/micromachines
Micromachines 2023,14, 1520 2 of 29
of contaminated water and skin contact [
10
]. Heavy metals are responsible for a plethora
of diseases, such as cancer, diseases of the immune system, kidney failure, allergies, heart
problems, neurodegenerative diseases, etc. [
11
14
]. In Figure 1, the severe impact of water
pollution by heavy metals on human health is depicted.
Micromachines 2023, 14, 1520 2 of 30
fauna and ora, catastrophic to animal and plant habitats and can eventually be lethal to
living organisms, including humans [8,9].
The ways through which heavy metals accumulate into the human body vary and
include inhalation from the atmosphere, the ingestion of contaminated food, the drinking
of contaminated water and skin contact [10]. Heavy metals are responsible for a plethora
of diseases, such as cancer, diseases of the immune system, kidney failure, allergies, heart
problems, neurodegenerative diseases, etc. [11–14]. In Figure 1, the severe impact of water
pollution by heavy metals on human health is depicted.
Figure 1. Schematic representation of the eects on human health due to water pollution by heavy
metals.
The need for clean and safe water can be addressed with the development of easy-to-
use, compact and portable devices targeting heavy metal ions detection. Microuidic de-
vices oer the possibility to manipulate minute volumes of uids (typically a few micro-
liters or less) in a way that makes it possible to perform chemical or biological analysis on
a single chip. They usually consist of a simple or complex network of microchannels and
microchambers, which serve as reaction chambers or reagent reservoirs. When this tech-
nology is applied to the detection of heavy metal ions, rapid and aordable devices with
reasonable accuracy can be foreseen [15]. LOCs are a subclass of microuidic devices that
strive to include on a single chip all the functions that are necessary to perform a full anal-
ysis of a sample in a much the same way as it is performed in a laboratory. In addition,
LOCs should preferably operate autonomously and be portable. Thus, LOCs can be con-
sidered microlaboratories with many advantages, including a small sample volume, re-
duced analysis time, low manufacturing cost and great sensitivity [1620]. Being a rela-
tively new technology, LOCs and microuidic devices in general are constantly open to
new technological approaches, and new materials play an important role in their devel-
opment. Materials such as glass, silicon, paper, polydimethylsiloxane (PDMS), poly(me-
thyl methacrylate) (PMMA), cyclic olen copolymer (COC), polyethylene terephthalate
(PET), polyvinyl chloride (PVC), polycarbonate (PC) and 3D printing materials are usu-
ally used for the fabrication of microuidics [21]. Silicon and glass were the rst-genera-
tion materials for microuidics as they are thoroughly characterized materials with good
surface properties and a wide range of well-established processing techniques, while glass
has also excellent optical transparency and biocompatibility. Nevertheless, these materials
Figure 1.
Schematic representation of the effects on human health due to water pollution by
heavy metals.
The need for clean and safe water can be addressed with the development of easy-
to-use, compact and portable devices targeting heavy metal ions detection. Microfluidic
devices offer the possibility to manipulate minute volumes of fluids (typically a few mi-
croliters or less) in a way that makes it possible to perform chemical or biological analysis
on a single chip. They usually consist of a simple or complex network of microchannels
and microchambers, which serve as reaction chambers or reagent reservoirs. When this
technology is applied to the detection of heavy metal ions, rapid and affordable devices
with reasonable accuracy can be foreseen [
15
]. LOCs are a subclass of microfluidic devices
that strive to include on a single chip all the functions that are necessary to perform a
full analysis of a sample in a much the same way as it is performed in a laboratory. In
addition, LOCs should preferably operate autonomously and be portable. Thus, LOCs
can be considered microlaboratories with many advantages, including a small sample
volume, reduced analysis time, low manufacturing cost and great sensitivity [
16
20
]. Being
a relatively new technology, LOCs and microfluidic devices in general are constantly open
to new technological approaches, and new materials play an important role in their devel-
opment. Materials such as glass, silicon, paper, polydimethylsiloxane (PDMS), poly(methyl
methacrylate) (PMMA), cyclic olefin copolymer (COC), polyethylene terephthalate (PET),
polyvinyl chloride (PVC), polycarbonate (PC) and 3D printing materials are usually used
for the fabrication of microfluidics [
21
]. Silicon and glass were the first-generation mate-
rials for microfluidics as they are thoroughly characterized materials with good surface
properties and a wide range of well-established processing techniques, while glass has also
excellent optical transparency and biocompatibility. Nevertheless, these materials require
cleanroom facilities and sophisticated equipment to process, thus rendering the fabrication
of LOCs expensive. However, PDMS and thermoplastics, like PMMA, PVC, etc., are com-
monly used as they are relatively inexpensive and well researched. In particular, PDMS is a
material with the following advantages: it is biocompatible, cheap, optically transparent,
easy to mold and good for prototyping. Paper microfluidics are characterized by a low cost
and can be used to measure desired molecules quickly via visual inspection [22,23].
Micromachines 2023,14, 1520 3 of 29
In addition, LOCs are versatile devices, which can be combined with different detection
methods allowing their application in many areas, such as proteomics, gene research, point
of care (POC), analytical chemistry, environmental monitoring (heavy metal ions and
pesticide detection), food safety [
24
33
] and other relevant industrial applications (i.e.,
liquid–liquid extraction) [34,35].
The fabrication of such innovative microfluidic devices enables the development of
portable devices for on-site analysis [
36
] and can revolutionize the way sciences, such as
analytical chemistry and biology, are used. Although conventional spectroscopic tech-
niques, such as atomic absorption spectroscopy (AAS), inductively coupled plasma mass
spectroscopy (ICP-MS) or other analytical methods, like high-performance liquid chro-
matography (HPLC), are currently the gold standard for such analyses due to their high
accuracy and sensitivity, they cannot meet the specifications for portability, since most
of them require bulky and expensive equipment and highly trained personnel and are
time-consuming [4,37].
This review paper is focused on providing a comprehensive literature overview of the
most recent and promising examples of microfluidic and LOC devices used for the detection
of the most important toxic metal ions, namely, lead, mercury, arsenic, cadmium and
chromium. Emphasis is given to the fabrication methods, the materials used, the detection
methods proposed and their sensitivity, focusing on highlighting the most promising
approaches that already exist in the literature. It is additionally intended to present the
limitations of the state-of-the-art examples as well as the challenges in the field. Our study
shows that several devices can meet the regulation limits of detection, but few of them
have passed to the commercial phase. The reasons for this slow uptake of new detection
methods and devices are also discussed at the end of this manuscript.
2. Microfluidic and Lab-on-Chip Devices for Heavy Metal Ions Detection Using
Various Detection Methods
Integrated microfluidic devices enable the transfer of most processes performed on a
laboratory bench to a single device, and, in this way, they can meet the requirements of
POC systems (Figure 2) [38].
To the question of what drives this extensive research and development of new micro
total analysis systems (
µ
TAS), or lab-on-chip devices, the answer is the development of
micro- and nanotechnology, new materials, and smaller, smarter and more efficient elec-
tronic systems. For example, new nanomaterials offer improved sensing properties, greater
sensitivity and greater selectivity. Thus, for the fabrication of innovative LOC devices,
special attention must be paid to the choice of the materials used for the fabrication of
the sensor that is integrated into the LOC devices. Novel materials, including nanoma-
terials, are utilized for the sensors’ fabrication for the detection of heavy metals. Some
good examples are carbon nanotubes, graphene, reduced graphene oxide and carbon dots
(CDs) and polymeric materials (e.g., Polyaniline (PANI), Nafion, Poly(ethylene glycol)
(PEG), Poly(vinyl alcohol) (PVA)), as well as metal nanoparticles (e.g., gold, silver, copper)
and metal oxides (e.g., CuO, MgO, ZnO, MnO2, Fe3O4, SNO2, TiO2and ZrO2) [3,6,3941].
Another common approach is to combine bioreceptors with some of the aforementioned
materials for the fabrication of novel sensors in which the detection mechanism is related
to the biological molecules’ type (e.g., enzymes, antibodies, DNA, RNA, etc.), resulting in
the fabrication of immunosensors and aptamer-based and enzyme-based sensors [
5
]. The
development of such nanomaterials with improved electrical and mechanical properties
and the development and innovation in the area of microfabrication can transform LOC
devices into powerful devices [42].
At the same time, the selected detection scheme is a very important part of the
integrated lab-on-chip or microfluidic device. The main goal is to develop portable, low-cost
and easy-to-fabricate and -operate devices that can be used in the point of interest [
43
], and
this is the reason for the rise in alternative detection methods. To this end, several detection
methods have been proposed to be used in combination with microfluidics in order to
Micromachines 2023,14, 1520 4 of 29
provide portable detection devices. Examples of the sensors that have been proposed
for the detection of heavy metal ions are the following: electrochemical, fluorescence,
colorimetric, (electro)chemiluminescence, piezoresistive, surface plasmon resonance (SPR)
and surface-enhanced Raman scattering (SERS) sensors [
15
,
44
48
]. Figure 3shows a
schematic representation of the different materials and fabrication and detection methods
that can be combined for the fabrication of microfluidic devices.
Micromachines 2023, 14, 1520 4 of 30
Figure 2. Illustration of miniaturized and integrated microuidic devices for POC diagnosis. Repro-
duced with permission from reference [38].
To the question of what drives this extensive research and development of new micro
total analysis systems TAS), or lab-on-chip devices, the answer is the development of
micro- and nanotechnology, new materials, and smaller, smarter and more ecient elec-
tronic systems. For example, new nanomaterials oer improved sensing properties,
greater sensitivity and greater selectivity. Thus, for the fabrication of innovative LOC de-
vices, special aention must be paid to the choice of the materials used for the fabrication
of the sensor that is integrated into the LOC devices. Novel materials, including nano-
materials, are utilized for the sensors fabrication for the detection of heavy metals. Some
good examples are carbon nanotubes, graphene, reduced graphene oxide and carbon dots
(CDs) and polymeric materials (e.g., Polyaniline (PANI), Naon, Poly(ethylene glycol)
(PEG), Poly(vinyl alcohol) (PVA)), as well as metal nanoparticles (e.g., gold, silver, copper)
and metal oxides (e.g., CuO, MgO, ZnO, MnO2, Fe3O4, SNO2, TiO2 and ZrO2) [3,6,39–41].
Another common approach is to combine bioreceptors with some of the aforementioned
materials for the fabrication of novel sensors in which the detection mechanism is related
to the biological molecules type (e.g., enzymes, antibodies, DNA, RNA, etc.), resulting in
the fabrication of immunosensors and aptamer-based and enzyme-based sensors [5]. The
development of such nanomaterials with improved electrical and mechanical properties
and the development and innovation in the area of microfabrication can transform LOC
devices into powerful devices [42].
At the same time, the selected detection scheme is a very important part of the inte-
grated lab-on-chip or microuidic device. The main goal is to develop portable, low-cost
and easy-to-fabricate and -operate devices that can be used in the point of interest [43],
and this is the reason for the rise in alternative detection methods. To this end, several
Figure 2.
Illustration of miniaturized and integrated microfluidic devices for POC diagnosis. Repro-
duced with permission from reference [38].
Electrochemical sensors [
15
,
44
,
45
] offer high sensitivity, a low limit of detection (LOD)
and real-time detection results. Such sensors are ideal for water safety applications, since
water pollutants monitoring can be achieved via changes in the electrical response, as
the pollutants affect the electrical signal [
46
]. The most popular electrochemical methods
combined with microfluidic devices are based on amperometry, conductometry, potentiom-
etry and voltammetry. Electrochemical sensors also include resistive sensors, in which
the response is based on resistance changes or differences, and capacitive-type sensors,
in which the device capacity is measured. Furthermore, electrochemical impedance spec-
troscopy (EIS) is also used for heavy metals ions detection since it is a simple, rapid and
low-cost technique. One of the methods that has been widely used for the fabrication
of electrochemical sensors intended for environmental monitoring is screen-printing, as
reported in the literature [49,50].
Optical methods, like fluorescence, colorimetric methods and surface-enhanced Raman
scattering (SERS) spectroscopy, are also very common for heavy metals detection as they
have a relatively good sensitivity and specificity and they can be easily combined with
microfluidic devices to enable devices suitable for POC applications. Optical methods based
on fluorescence, although they are rapid, sensitive, non-destructive and can be employed for
in situ or in-line monitoring, usually require more sophisticated external equipment. This
Micromachines 2023,14, 1520 5 of 29
equipment used to be bulky and less portable, but nowadays several portable fluorescence
sensors exist [
51
]. Colorimetric methods, however, are usually combined with microfluidic
paper-based devices used in water safety for heavy metals detection. Such methods are
related to the change in color in the presence of the analyte. In this way, colorimetric
methods facilitate the direct detection of heavy metals (liquids or solids) by the naked eye,
whereas an optical system can be used for further analysis. This method offers qualitative
results in a simple and facile way. Again, in order to achieve the quantification of the results
and reach a low LOD, coupling with an image analysis software or device is required,
which is nowadays trivial through the wide use of smart portable devices (i.e., mobile
phones) [15,47].
Micromachines 2023, 14, 1520 5 of 30
detection methods have been proposed to be used in combination with microuidics in
order to provide portable detection devices. Examples of the sensors that have been pro-
posed for the detection of heavy metal ions are the following: electrochemical, uores-
cence, colorimetric, (electro)chemiluminescence, piezoresistive, surface plasmon reso-
nance (SPR) and surface-enhanced Raman scaering (SERS) sensors [15,4448]. Figure 3
shows a schematic representation of the dierent materials and fabrication and detection
methods that can be combined for the fabrication of microuidic devices.
Figure 3. Schematic representation of the materials and the fabrication and detection methods that
are used for the realization of microuidic devices intended for heavy metal ions detection.
Electrochemical sensors [15,44,45] oer high sensitivity, a low limit of detection
(LOD) and real-time detection results. Such sensors are ideal for water safety applications,
since water pollutants monitoring can be achieved via changes in the electrical response,
as the pollutants aect the electrical signal [46]. The most popular electrochemical meth-
ods combined with microuidic devices are based on amperometry, conductometry, po-
tentiometry and voltammetry. Electrochemical sensors also include resistive sensors, in
which the response is based on resistance changes or dierences, and capacitive-type sen-
sors, in which the device capacity is measured. Furthermore, electrochemical impedance
spectroscopy (EIS) is also used for heavy metals ions detection since it is a simple, rapid
and low-cost technique. One of the methods that has been widely used for the fabrication
of electrochemical sensors intended for environmental monitoring is screen-printing, as
reported in the literature [49,50].
Optical methods, like uorescence, colorimetric methods and surface-enhanced Ra-
man scaering (SERS) spectroscopy, are also very common for heavy metals detection as
they have a relatively good sensitivity and specicity and they can be easily combined
with microuidic devices to enable devices suitable for POC applications. Optical meth-
ods based on uorescence, although they are rapid, sensitive, non-destructive and can be
employed for in situ or in-line monitoring, usually require more sophisticated external
equipment. This equipment used to be bulky and less portable, but nowadays several
portable uorescence sensors exist [51]. Colorimetric methods, however, are usually com-
bined with microuidic paper-based devices used in water safety for heavy metals detec-
tion. Such methods are related to the change in color in the presence of the analyte. In this
way, colorimetric methods facilitate the direct detection of heavy metals (liquids or solids)
Figure 3.
Schematic representation of the materials and the fabrication and detection methods that
are used for the realization of microfluidic devices intended for heavy metal ions detection.
SERS is used for the detection of targets on the single-molecule level on the surface
using noble metal (e.g., Au, Ag and Cu) nanostructures. SERS is characterized by a high
sensitivity and selectivity, less sample pretreatment, a simple operation, a short response
time and rich spectral fingerprint information [
15
,
44
,
52
]. Another optical method used for
heavy metals detection is SPR [
43
,
53
]. SPR has a simple design and high sensitivity, is label
free, offers a real-time response and is of low cost.
The rapid growth of chemiluminescence (CL) techniques in the last decades has
also led to their use in the detection of different analyte targets including heavy metals
amongst others. CL is similar to the fluorescent method and is characterized by high
sensitivity. In addition, CL requires simple instrumentation when compared to other optical
detection methods, but is restricted by the reagents required (i.e., luminol and ruthenium
complexes) and is influenced by the solution composition, its pH and temperature, which
can affect reproducibility.
Finally, in some cases microfluidic devices are integrated with piezoresistive sensors
in order to fabricate a portable device for rapid heavy metals detection. This kind of sensor
relies on a change in electrical resistance under mechanical strain [
54
]. In the following
sections, an overview of these efforts is presented for each one of the most important heavy
metal ions.
Micromachines 2023,14, 1520 6 of 29
2.1. Lead (Pb) Detection
Lead (Pb) is one of the most dangerous heavy metals that can be found in the environ-
ment. It is released by chemical pollution and industrial activities, whereas pollution in
drinking water is usually caused by plumbing materials. Some of the negative effects of
Pb on humans are that it can act on the nervous system and on skeletal development and
it can cause anemia, hypertension, obesity, arrhythmia, kidney failure and even immune
system dysfunctions. The fact that even in small amounts Pb
2+
can inflict damage on adults
and children, infants and fetuses especially, stresses the need for Pb
2+
detection [
44
,
46
].
Several examples have been reported in the literature for microfluidic devices combined
with optical and electrochemical detection systems for the detection of Pb.
For example, K. A. Shaikh et al. [
55
] have developed a simple and low-cost LOC system,
which incorporates channels, reaction chambers, sensors and actuators for Pb2+ detection.
By using a DNAzyme fluorescent biosensor, they manage to detect Pb
2+
concentrations
from 10
µ
M to 500 nM. The DNAzyme scheme has also been used in another work for real-
time Pb
2+
detection, by utilizing fluorescent tags on the DNAzyme, which are immobilized
inside a PMMA-based microfluidic device [
56
]. A microfluidic device with a passive mixer
and fluorescent molecular sensors based on calixarene systems for selective Pb
2+
detection
in water is presented in [
57
]. Using a PDMS Y-shape microchannel bonded on a glass
substrate via oxygen plasma treatment, they achieved the detection of 5 ppb of Pb
2+
. A
portable and power-free PDMS microfluidic device based on 11-mercaptoundecanoic acid-
functionalized gold nanoparticles for Pb
2+
detection is reported in [
58
]. The detection is
achieved using a microscope or a water drop as a magnifier, and 10
µ
M of Pb
2+
are detected
by this scheme.
W. H. Huang et al. [
59
] have fabricated a PDMS microfluidic device based on graphene
oxide (GO)/aptamer sensors for the simultaneous detection of Hg
2+
and Pb
2+
ions. They
have achieved the detection of concentrations of around 0.70 ppb and 0.53 ppb for Hg
2+
and Pb
2+
, respectively, which are lower than those proposed by the World Health Orga-
nization (WHO) (Figure 4). An alternative method for Pb
2+
detection is achieved using a
microfluidic analogue of Wheatstone-bridge (SMAW) with a microgel [
60
]. In particular,
the PDMS/glass-based SMAW microchip allows signal conversion and amplification for
the real-time continuous detection of Pb
2+
, with a detection limit of 10
14
M, utilizing an
optical microscope.
Micromachines 2023, 14, 1520 7 of 30
amplication for the real-time continuous detection of Pb2+, with a detection limit of 1014
M, utilizing an optical microscope.
Figure 4. Schematic representation of the measurement system used for the detection of Hg2+ (0.70
ppb) and Pb2+ (0.53 ppb) inside a PDMS microuidic device. The GO/aptamer suspension and the
metal ion solutions are introduced inside the microuidic device through the two inlets of the device
using a syringe pump. The detection is achieved via the GO/aptamer suspension uorescence in-
tensity change, while the quenching eect is evaluated via image analysis software installed on an
interfaced PC. Reproduced with permission from reference [59]. This article is an open-access article
distributed under the terms and conditions of the Creative Commons Aribution (CC BY) license.
Another promising portable and low-cost platform is presented in [61]. In particular,
a paper-based microuidic device for heavy metal ions detection using DNA strands and
electrochemiluminescence (ECL) labels was fabricated. In this way, they have achieved
the simultaneous detection of 10 pM Pb2+ and 0.2 nM Hg2+. N. Fakhri et al. [62] have also
proposed a paper-based microuidic for lead detection in water. They have combined ap-
tamers with gold nanoparticles for the colorimetric detection of Pb2+, and, using two types
of lter paper, namely, Whatman No. 1 and nylon lter papers, they have detected 1.2 nM
and 0.7 nM of Pb2+, respectively. Furthermore, a microuidic paper-based analytical de-
vice (µPAD) has been proposed in which lead detection is either performed via naked eye
estimation of the color change on the pad (principle 1) or using image analysis for the
color change intensity (principle 2) [63]. A sodium rhodizonate reagent (NaR) is used in
both approaches and after the injection of the sample a color change is observed; while
using principle 1, the limit of detection is 0.756 mg L1.
In addition, J. Zhou et al. [64] have fabricated a portable paper-based device for heavy
metals detection with quantitative information, resulting in a promising platform for the
rapid testing of metal ions. In this approach, ZnSe quantum dots (QDs) are combined with
ion imprinted polymers (IIPs) for the detection of Cd2+ and Pb2+ ions with detection limits
of 0.245 µg L1 and of 0.335 µg L1, respectively. Finally, a cloth/paper hybrid microuidic
analytical device with a uorescence sensing cloth-based component has been proposed
for the detection of Hg2+ and Pb2+ ions with concentrations down to 0.18 and 0.07 µg L1,
respectively [65]. For the realization of this uorescence sensing cloth-based component,
which is assembled on a rotary µPAD substrate, rst quantum dots are grafted onto the
coon cloth and then IIPs are used for further modication. While using this scheme, they
have managed to optimize the portability of the device.
Figure 4.
Schematic representation of the measurement system used for the detection of Hg
2+
(0.70 ppb) and Pb
2+
(0.53 ppb) inside a PDMS microfluidic device. The GO/aptamer suspension and
Micromachines 2023,14, 1520 7 of 29
the metal ion solutions are introduced inside the microfluidic device through the two inlets of the
device using a syringe pump. The detection is achieved via the GO/aptamer suspension fluorescence
intensity change, while the quenching effect is evaluated via image analysis software installed on an
interfaced PC. Reproduced with permission from reference [
59
]. This article is an open-access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Another promising portable and low-cost platform is presented in [
61
]. In particular,
a paper-based microfluidic device for heavy metal ions detection using DNA strands and
electrochemiluminescence (ECL) labels was fabricated. In this way, they have achieved
the simultaneous detection of 10 pM Pb
2+
and 0.2 nM Hg
2+
. N. Fakhri et al. [
62
] have also
proposed a paper-based microfluidic for lead detection in water. They have combined
aptamers with gold nanoparticles for the colorimetric detection of Pb
2+
, and, using two
types of filter paper, namely, Whatman No. 1 and nylon filter papers, they have detected
1.2 nM and 0.7 nM of Pb
2+
, respectively. Furthermore, a microfluidic paper-based analytical
device (
µ
PAD) has been proposed in which lead detection is either performed via naked
eye estimation of the color change on the pad (principle 1) or using image analysis for the
color change intensity (principle 2) [
63
]. A sodium rhodizonate reagent (NaR) is used in
both approaches and after the injection of the sample a color change is observed; while
using principle 1, the limit of detection is 0.756 mg L1.
In addition, J. Zhou et al. [
64
] have fabricated a portable paper-based device for heavy
metals detection with quantitative information, resulting in a promising platform for the
rapid testing of metal ions. In this approach, ZnSe quantum dots (QDs) are combined with
ion imprinted polymers (IIPs) for the detection of Cd
2+
and Pb
2+
ions with detection limits
of 0.245
µ
g L
1
and of 0.335
µ
g L
1
, respectively. Finally, a cloth/paper hybrid microfluidic
analytical device with a fluorescence sensing cloth-based component has been proposed
for the detection of Hg
2+
and Pb
2+
ions with concentrations down to 0.18 and 0.07
µ
g L
1
,
respectively [
65
]. For the realization of this fluorescence sensing cloth-based component,
which is assembled on a rotary
µ
PAD substrate, first quantum dots are grafted onto the
cotton cloth and then IIPs are used for further modification. While using this scheme, they
have managed to optimize the portability of the device.
Many attempts have also been reported in the literature for paper-based microfluidic
devices that are combined with electrochemical detection systems. Such systems can be
more versatile and more quantitative. Z. Nie et al. [
66
] have described a paper-based
microfluidic device in which the screen-printed electrodes (SPEs) made from conducting
inks, like carbon or Ag/AgCl, are fabricated on paper or polyester film for Pb
2+
detection.
Furthermore, M. Medina-Sánchez et al. [
67
] have fabricated a portable lab-on-paper device,
which also allows sample pretreatment for the electrochemical sensing of lead and cadmium
with concentrations down to 7 and 11 ppb, respectively. The device was fabricated using
wax and screen-printing technologies. A miniaturized paper-based microfluidic device
with a three-dimensional layout with working and counter electrodes using a graphite foil
was used for Cd
2+
and Pb
2+
detection, and this electrochemical-based microfluidic device
can detect concentrations down to 1.2
µ
g L
1
and 1.8
µ
g L
1
, respectively (Figure 5) [
68
].
In another approach, a boron-doped diamond paste electrode, which can be stencil-printed,
was combined with paper-based microfluidic devices for the realization of a low-cost,
high-performance electrochemical sensor for the detection of Pb
2+
and Cd
2+
[
69
]. The
detection limit of this device is 1 and 25 ppb for Pb2+ and Cd2+, respectively.
W. Jung et al. [
70
] have fabricated a miniaturized polymer lab chip sensor that is
reusable, using microfabrication technology for the continuous and on-site detection of
heavy metals and especially Pb
2+
. The device consists of a microfluidic channel and a fully
integrated sensor with a planar Ag working electrode and Ag counter/quasi-reference. The
LOD was measured via square-wave anodic stripping voltammetry (SWASV) and it was
found to be 0.55 ppb. A transparent integrated microfluidic device with a 3D-printed thin-
layer flow cell (3D-PTLFC) and an S-shaped SPE for heavy metal ion stripping analysis is
presented in [
71
]. This device has a high performance and is characterized by a low cost, and
the LOD for Pb
2+
is 0.3
µ
g L
1
. An electrochemical system using 3D-PTLFC and a flow-field
Micromachines 2023,14, 1520 8 of 29
shaped solid electrode (FFSSE) was used for Pb
2+
detection (Figure 6A) [
72
]. This square-
wave anodic stripping voltammetry (ASV) system is characterized by a better sensitivity
and reproducibility compared to a traditional ASV-based method with a detection limit
of 0.2
µ
g L
1
(0.2 ppb). B. Ding et al. [
73
] have fabricated a 3D-printed flow reactor in
which porous carbon electrodes made via direct laser sintering on polymer films are placed.
This scheme is used for Pb
2+
detection with an LOD of 0.0330 mg L
1
. A. Chałupniak
et al. [
74
] have fabricated a LOC platform that consists of a screen-printed carbon electrode
(SPCE), a PDMS chip and a GO–PDMS chip for the preconcentration and detection of heavy
metals like Pb
2+
. Another lab-on-chip device in which a 3D-printed microfluidic device is
combined with an epitaxial graphene (EG) sensor was fabricated for Pb
2+
electrochemical
detection [
75
] (Figure 6B). The authors reported a quite low LOD of 95 nM for Pb
2+
,
which is attributed to the high sensitivity of the sensing material. In addition, a portable
resistive device for the detection of Pb
2+
in water, with an LOD of 0.81 nM and a shelf-
life of
~45 days
, was reported in [
76
]. For the realization of this device, they combined
miniaturized electronics with a microfluidic well, while the sensing material is based on
α-MnO2/GQD nanocomposites.
Furthermore, J. Dai et al. [
77
] have reported an integrated and miniaturized microflu-
idic electrochemical sensor for Pb
2+
detection. For the fabrication of the device, a “glass-
silicon-glass” sandwich structure was developed, while the microsensor has a nanochannel
liquid conjunct Ag/AgCl reference electrode, a working electrode with a three-dimensional
Au micropillar array and a detection chamber for sample measurement. Finally, the device
is characterized by a good sensitivity, repeatability and selectivity and a wide detection
range, enabling its use for water quality monitoring, and its LOD is
0.13 µg L1
. In another
work, a microfluidic device with an electrochemical carbon sensor was used for Pb
2+
detec-
tion, since this kind of sensor decreases the LOD, which is 40 ppt, by three orders compared
to traditional heavy metal sensors.
Micromachines 2023, 14, 1520 8 of 30
Many aempts have also been reported in the literature for paper-based microuidic
devices that are combined with electrochemical detection systems. Such systems can be
more versatile and more quantitative. Z. Nie et al. [66] have described a paper-based mi-
crouidic device in which the screen-printed electrodes (SPEs) made from conducting
inks, like carbon or Ag/AgCl, are fabricated on paper or polyester lm for Pb2+ detection.
Furthermore, M. Medina-Sánchez et al. [67] have fabricated a portable lab-on-paper de-
vice, which also allows sample pretreatment for the electrochemical sensing of lead and
cadmium with concentrations down to 7 and 11 ppb, respectively. The device was fabri-
cated using wax and screen-printing technologies. A miniaturized paper-based microu-
idic device with a three-dimensional layout with working and counter electrodes using a
graphite foil was used for Cd2+ and Pb2+ detection, and this electrochemical-based micro-
uidic device can detect concentrations down to 1.2 µg L1 and 1.8 µg L1, respectively
(Figure 5) [68]. In another approach, a boron-doped diamond paste electrode, which can
be stencil-printed, was combined with paper-based microuidic devices for the realiza-
tion of a low-cost, high-performance electrochemical sensor for the detection of Pb2+ and
Cd2+ [69]. The detection limit of this device is 1 and 25 ppb for Pb2+ and Cd2+, respectively.
Figure 5. Illustration of a paper-based (light blue) microfluidic device with graphite foil (black) for Cd2+
and Pb2+ monitoring. The electrodes are placed on a PMMA substrate to facilitate operation. This de-
vice with the carbon-based sensor has a three-dimensional layout in which the counter and the work-
ing electrodes are facing each other and as a result the microfluidic paper channel is placed among
these two electrodes. A piece of sponge is used as analyte reservoir and an absorbent pad is placed on
the channel end and capillary flow is enabled. Reproduced with permission from reference [68]. This
is an open-access article published under an ACS AuthorChoice License, which permits the copying
and redistribution of the article or any adaptations for non-commercial purposes.
W. Jung et al. [70] have fabricated a miniaturized polymer lab chip sensor that is re-
usable, using microfabrication technology for the continuous and on-site detection of
heavy metals and especially Pb2+. The device consists of a microuidic channel and a fully
integrated sensor with a planar Ag working electrode and Ag counter/quasi-reference.
The LOD was measured via square-wave anodic stripping voltammetry (SWASV) and it
was found to be 0.55 ppb. A transparent integrated microuidic device with a 3D-printed
thin-layer ow cell (3D-PTLFC) and an S-shaped SPE for heavy metal ion stripping anal-
ysis is presented in [71]. This device has a high performance and is characterized by a low
cost, and the LOD for Pb2+ is 0.3 µg L1. An electrochemical system using 3D-PTLFC and a
ow-eld shaped solid electrode (FFSSE) was used for Pb2+ detection (Figure 6A) [72]. This
square-wave anodic stripping voltammetry (ASV) system is characterized by a beer sen-
sitivity and reproducibility compared to a traditional ASV-based method with a detection
limit of 0.2 µg L1 (0.2 ppb). B. Ding et al. [73] have fabricated a 3D-printed ow reactor in
which porous carbon electrodes made via direct laser sintering on polymer lms are
placed. This scheme is used for Pb2+ detection with an LOD of 0.0330 mg L1. A. Chałupniak
Figure 5.
Illustration of a paper-based (light blue) microfluidic device with graphite foil (black) for
Cd
2+
and Pb
2+
monitoring. The electrodes are placed on a PMMA substrate to facilitate operation.
This device with the carbon-based sensor has a three-dimensional layout in which the counter and
the working electrodes are facing each other and as a result the microfluidic paper channel is placed
among these two electrodes. A piece of sponge is used as analyte reservoir and an absorbent pad
is placed on the channel end and capillary flow is enabled. Reproduced with permission from
reference [
68
]. This is an open-access article published under an ACS AuthorChoice License, which
permits the copying and redistribution of the article or any adaptations for non-commercial purposes.
A novel autonomous robotic system for Pb
2+
detection in surface water has been devel-
oped [
78
]. More specifically, a microfluidic device was combined with an electrochemical
sensor made from carbon-based screen-printed electrodes. The device has the ability of
performing 39 measurements per day, and the limit of detection for Pb
2+
for this integrated
system is 4
µ
g L
1
(Figure 6C). M. Zhang et al. [
79
] have proposed a chip consisting of
Micromachines 2023,14, 1520 9 of 29
an electrochemical sensor and a digital microfluidic (DMF) platform for the detection of
Pb
2+
in tap water (Figure 6D). This portable device has a low power consumption and
relay control modules, it enables automatic sample pretreatment, sensing, waste collection
and data acquisition, and the sensing node can be functional for several years using a
normal battery. Another example of a microfluidic device with an electrochemical sensor
is presented in [
80
]. In particular, a 3D Ag-rGO-f-Ni(OH)
2
/NF composite is utilized as
an amplifier of the electrochemical signals under the synergistic effect of thermocapillary
convection, with which an acceleration of the preconcentration process and reduction
in the detection time (it saves 300 s of preconcentration time) is achieved. This portable
device is controlled by a smartphone and the LOD of Pb
2+
in river water is 0.00498
µ
g L
1
.
Finally, a microfluidic channel was combined with a wireless sensor in a low-temperature
cofired ceramic substrate among the capacitor plates for the detection of various metals
ions, like Pb(NO
3
)
2
and Cd(NO
3
)
2
(Figure 6E) [
81
]. Thus, via the changes in the amplitude
of reflection coefficient, the detection of metal ion solutions in a low concentration range of
0–5 mM can be obtained, and the LOD of this kind of sensor can be as low as 5 µM.
2.2. Mercury (Hg) Detection
Mercury (Hg) is another harmful pollutant that affects the environment, and it is
produced by various industries, such as the paper, pharmaceuticals and horticulture
industries. It can be absorbed by fish or shellfish and enter to human body via the food
chain or by drinking water, affecting in this way cardiovascular, gastrointestinal, urinary
and neurological systems. The toxicity of Hg and its compounds differs according to the
method of inhalation or ingestion or the amount. The provisional tolerable weekly intake of
Hg in foods proposed by the Food and Agriculture Organization of the United Nations and
the WHO is 0.3 mg. No detectable negative effects are caused to the human body below
this limit, but this high safety standard stresses the need for accurate Hg detection [44,46].
Similarly to Pb
2+
, many efforts have been made for the detection of Hg using microflu-
idics devices and optical detection systems. For example, Hg
2+
was detected via an optical
microfluidic device with ionophore modified gold nanoparticles [
82
]. This device, which
uses an easy and automated procedure, is selective to Hg
2+
among different ions that may
exist in environmental water samples, with an LOD of 11 ppb. Guilong Peng et al. [
83
]
have achieved the detection of 0.031
µ
M of Hg
2+
using a microfluidic chip, fabricated
after the bonding of PDMS with a cleaned glass slide via an oxygen plasma treatment
step. The chip is then integrated with on-line complexing and laser-induced fluorescence
detection. The device is based on a rhodamine derivative (RD), which is the fluorescent
chemosensor and thus, by combining the microfluidic technology with the chemosensor,
they have developed a portable and low-cost device with less consumption of sample and
reagents, high selectivity and a rapid response time, demonstrating the potential in on-site
analysis. In addition, a digital microfluidic fluorometric sensor was proposed for Hg
2+
detection in costal seawater [
84
]. As previously discussed, a rhodamine-based fluorescent
probe is used for the detection of Hg
2+
due to its fast response at ambient temperatures and
high selectivity in Hg
2+
, and by changing the sensitive fluorescent probe other metals like
Pb and Cd can also be detected. This rapid and low-cost device enabled the detection of
mercury with a concentration down to 1.4 ppb. Another example for the detection of toxic
metals is the use of CDs as the selective optical reagents in a microanalyzer consisting of a
COC analytical microsystem, a flow management system and a miniaturized customized
optical detection system (Figure 7) [
85
]. By utilizing this device, they have managed to
detect various heavy metals ions such as Hg
2+
and Pb
2+
with detection limits ranging from
2 to 12 ppb and even lower for Hg2+.
Micromachines 2023,14, 1520 10 of 29
Micromachines 2023, 14, 1520 9 of 30
et al. [74] have fabricated a LOC platform that co nsist s of a scre en- printed carbon electrode
(SPCE), a PDMS chip and a GO–PDMS chip for the preconcentration and detection of
heavy metals like Pb2+. Another lab-on-chip device in which a 3D-printed microuidic de-
vice is combined with an epitaxial graphene (EG) sensor was fabricated for Pb2+ electro-
chemical detection [75] (Figure 6B). The authors reported a quite low LOD of 95 nM for
Pb2+, which is aributed to the high sensitivity of the sensing material. In addition, a port-
able resistive device for the detection of Pb2+ in water, with an LOD of 0.81 nM and a shelf-
life of ~45 days, was reported in [76]. For the realization of this device, they combined
miniaturized electronics with a microuidic well, while the sensing material is based on
α-MnO2/GQD nanocomposites.
Furthermore, J. Dai et al. [77] have reported an integrated and miniaturized micro-
uidic electrochemical sensor for Pb2+ detection. For the fabrication of the device, a “glass-
silicon-glass” sandwich structure was developed, while the microsensor has a nanochan-
nel liquid conjunct Ag/AgCl reference electrode, a working electrode with a three-dimen-
sional Au micropillar array and a detection chamber for sample measurement. Finally, the
device is characterized by a good sensitivity, repeatability and selectivity and a wide de-
tection range, enabling its use for water quality monitoring, and its LOD is 0.13 µg L1. In
another work, a microuidic device with an electrochemical carbon sensor was used for
Pb2+ detection, since this kind of sensor decreases the LOD, which is 40 ppt, by three orders
compared to traditional heavy metal sensors.
A novel autonomous robotic system for Pb2+ detection in surface water has been de-
veloped [78]. More specically, a microuidic device was combined with an electrochem-
ical sensor made from carbon-based screen-printed electrodes. The device has the ability
of performing 39 measurements per day, and the limit of detection for Pb2+ for this inte-
grated system is 4 µg L1 (Figure 6C). M. Zhang et al. [79] have proposed a chip consisting
of an electrochemical sensor and a digital microuidic (DMF) platform for the detection
of Pb2+ in tap water (Figure 6D). This portable device has a low power consumption and
relay control modules, it enables automatic sample pretreatment, sensing, waste collection
and data acquisition, and the sensing node can be functional for several years using a
normal baery. Another example of a microuidic device with an electrochemical sensor
is presented in [80]. In particular, a 3D Ag-rGO-f-Ni(OH)2/NF composite is utilized as an
amplier of the electrochemical signals under the synergistic eect of thermocapillary
convection, with which an acceleration of the preconcentration process and reduction in
the detection time (it saves 300 s of preconcentration time) is achieved. This portable de-
vice is controlled by a smartphone and the LOD of Pb2+ in river water is 0.00498 µg L1.
Finally, a microuidic channel was combined with a wireless sensor in a low-temperature
cored ceramic substrate among the capacitor plates for the detection of various metals
ions, like Pb(NO3)2 and Cd(NO3)2 (Figure 6E) [81]. Thus, via the changes in the amplitude
of reection coecient, the detection of metal ion solutions in a low concentration range
of 05 mM can be obtained, and the LOD of this kind of sensor can be as low as 5 µM.
(A)
Micromachines 2023, 14, 1520 10 of 30
(B) (C)
(D) (E)
Figure 6. Examples of dierent microuidic devices proposed for heavy metal ions detection: (A)
An electrochemical sensor (FFSSE) combined with a 3D-PTLFC for Pb
2+
detection. Reproduced with
permission from reference [72]. (B) Schematic representation of a lab-on-chip device consisting of a
3D-printed microuidic device and an EG sensor for Pb
2+
detection. Reproduced with permission
from reference [75]. This article is an open-access article distributed under the terms and conditions
of the Creative Commons Aribution (CC BY) license. (C) (a,b) Images of an autonomous vehicle
for Pb
2+
detection in surface water and (c) illustration of the main parts of the microuidic device of
the particular system. Reproduced with permission from reference [78]. (D) The detection system
for Pb
2+
monitoring in tap water using a device comprising of DMF platform and an electrochemical
sensor. Reproduced with permission from reference [79]. (E) The measurement set up for Pb(NO
3
)
2
and Cd(NO
3
)
2
detection using a microuidic device. Reproduced with permission from reference
[81]. This is an open-access article distributed under the terms and conditions of the Creative Com-
mons Aribution CC-BY-NC-ND license.
2.2. Mercury (Hg) Detection
Mercury (Hg) is another harmful pollutant that aects the environment, and it is pro-
duced by various industries, such as the paper, pharmaceuticals and horticulture indus-
tries. It can be absorbed by sh or shellsh and enter to human body via the food chain or
by drinking water, aecting in this way cardiovascular, gastrointestinal, urinary and neu-
rological systems. The toxicity of Hg and its compounds diers according to the method
of inhalation or ingestion or the amount. The provisional tolerable weekly intake of Hg in
foods proposed by the Food and Agriculture Organization of the United Nations and the
Figure 6.
Examples of different microfluidic devices proposed for heavy metal ions detection: (
A
) An
electrochemical sensor (FFSSE) combined with a 3D-PTLFC for Pb
2+
detection. Reproduced with
permission from reference [
72
]. (
B
) Schematic representation of a lab-on-chip device consisting of a
3D-printed microfluidic device and an EG sensor for Pb
2+
detection. Reproduced with permission
from reference [
75
]. This article is an open-access article distributed under the terms and conditions of
the Creative Commons Attribution (CC BY) license. (
C
) (
a
,
b
) Images of an autonomous vehicle for
Pb
2+
detection in surface water and (
c
) illustration of the main parts of the microfluidic device of the
particular system. Reproduced with permission from reference [
78
]. (
D
) The detection system for Pb
2+
monitoring in tap water using a device comprising of DMF platform and an electrochemical sensor.
Reproduced with permission from reference [
79
]. (
E
) The measurement set up for Pb(NO
3
)
2
and
Cd(NO
3
)
2
detection using a microfluidic device. Reproduced with permission from reference [
81
].
This is an open-access article distributed under the terms and conditions of the Creative Commons
Attribution CC-BY-NC-ND license.
Paper-based microfluidics are constantly gaining ground in Hg
2+
monitoring. An
example of this case is presented in [
86
], in which they have managed to quantify mercury
ions using a distance-based detection method on a microfluidic portable and low-cost
µ
PAD.
Micromachines 2023,14, 1520 11 of 29
An insoluble colored complex is obtained when mercury ions interact with dithizone, and
mercury is quantified by measuring the length of the colored precipitate utilizing a printed
ruler along each device. A three-dimensional origami microfluidic paper-based chip for
fluorescence detection of Hg
2+
ions is reported in [
87
]. In particular, in this device CdTe QDs
are combined with ion imprinting technique resulting in a quantitative information and in a
detection limit of 0.056
µ
g L
1
. In another similar work, a three-dimensional microfluidic
paper-based device was presented as a solution for the detection of several metals (i.e.,
Cd
2+
, Pb
2+
, Hg
2+
) in coastal waters. The design of this device enabled a more homogeneous
permeation of the fluid in the paper chip, resulting in a 25-fold enrichment for each metal. The
reported LOD ranged from 0.007 to 0.015
µ
g L
1
for all metals tested [
88
]. K.
Patir et al
. [
89
]
have used nitrogen-doped carbon dots (NCDs) for fluorescence detection of Hg
2+
. Thus, by
fabricating a filter paper-based microfluidic device with NCDs they have achieved detections
of Hg
2+
with the concentration down to 0.1
µ
M. A chemically functionalized paper-based
microfluidic platform, in which silane compounds terminating in amine (NH
2
), carboxyl
(COOH) and thiol (SH) are immobilized on a patterned chromatography paper, has been
developed for the detection of various heavy metal ions, like Cr (VI) and Hg
2+
[
90
]. For
the quantification of the heavy metals detection, they used color intensity measurements,
and the LODs for Cr (VI) and Hg
2+
are 0.18 ppm and 0.19 ppm, respectively. Another
paper-based device, in which a smartphone is used as a colorimetric analyzer for monitoring
Hg
2+
in water samples, enabling use by unskilled users, is described in [
91
]. Using this
device with unmodified silver nanoparticles (AgNPs) on the detection zones, an LOD down
to Hg
2+
0.003 mg L
1
is achieved. G. Dindorkar et al. [
92
] have also considered that the
fabrication of a device for mercury detection is an imperative need. So, they have fabricated
a
µ
PAD, which is combined with a simple colorimetric android-based application, for Hg
2+
quantification with concentrations from 0.1g L
1
to 0.001 mg L
1
in water. The detection
scheme proposed included gold nanoparticles (AuNPs) functionalized with Papain and
2,6-pyridinedicarboxylic acid. A novel
µ
PAD device, which is combined with a colorimetric
sensor, was proposed for the detection of Hg
2+
ions in aqueous solutions [
93
]. In particular,
cysteamine@gold nanoparticles (CysA@AuNPs) are used with amino acids as ion detection
probes and Hg
2+
was detected via a naked eye color change for concentrations down to
0.001 ppm. In another example, a paper-based analytical device utilizing colorimetry for the
quantification of various metal ions such as Hg
2+
was also presented [
94
]. The metals are
monitored via the reaction between the metal ions and complexing agents in the detection
zone and the LOD of the proposed device for Hg
2+
is 0.20 mg L
1
. In another approach,
a paper disc device, which works with a compact smartphone-based reading device, was
proposed for the detection of water contaminants, such as Hg
2+
and Pb
2+
[
95
]. The method
is based on fluorescence, and concentrations down to 20 nM and 4 nM for Hg
2+
and Pb
2+
,
respectively, were detected.
A novel label-free device without the requirement of bulky equipment, enabling
portability, was reported in [
96
]. In particular, an SERS substrate in a PDMS microfluidic
channel, using silver nanostructures inside the microfluidic channel, for the rapid detection
of Hg ions compared to conventional SERS devices, was fabricated. This device can detect
Hg ions in aqueous solutions with a high sensitivity and good selectivity, and the reported
LOD is 1
×
10
7
M. W. Zhang et al. [
97
] have also achieved the detection of Hg
2+
using
a localized surface plasmon resonance (LSPR) nanosensor and a microfluidic chip made
from PDMS, which is bonded with a cover glass. This device, with nanostructures formed
by nanorods, can monitor Hg2+ in real-life water samples with an LOD of 2.7 pM.
Microfabrication technology for the fabrication of an on-chip integrated electrochem-
ical detector with planar electrodes (Au–Ag–Au three-electrode system) and a PDMS
microfluidic channel was utilized in reference [
98
]. In this way, a simple in use, low ana-
lyte consumption, rapid response, miniaturized device with a high sensitivity and good
reproducibility is developed for Hg
2+
monitoring. This device has an LOD of 3 ppb and
shows great potential for the application of in situ or on-line mercury detection. H. L.
Nguyen et al
. [
99
] have also combined a PDMS microfluidic chip with an electrochemical