Microfluidic Devices for the Detection of Contamination in

Water Samples: A Review

Prince Kumar Rai1, Monsur Islam2, Ankur Gupta1, *
1
Department of Mechanical Engineering, Indian Institute of Technology Jodhpur, 342037, India
2
Institute of Microstructure Technology, Karlsruhe Institute of Technology, Germany
*
Email of corresponding author: ankurgupta@iitj.ac.in

Abstract
Being a burgeoning environmental problem, water pollution becomes a worldwide apprehension due to
the inadequate accessibility of fresh water. Heavy metals, pharmaceuticals waste, organic, and inorganic
contaminants present in wastewater have shown significant threats to the environment and public health
globally. Currently available monitoring techniques involve complex equipment, longer processing time,
and highly skilled professionals, making these technique inadequate. Towards achieving a portable, highly
sensitive, and selective water quality control system, microfluidic devices have emerged as the technique
for the need of the hour. Several researchers have turned their attention to the microfluidic devices and
have been doing extensive research on the development and application of microfluidic-based devices for
the detection of water contaminants. Considering the fact that microfluidic devices have already marking
an impact in this field, this review article discusses latest development on the microfluidic-based water
quality control devices. This review summarizes popular fabrication approaches for microfluidic devices,
explored detection schemes, relevant fundamentals along with the state-of-the-art research work
performed on microfluidic devices for water contamination including heavy metals, organic, and inorganic
contaminants.

Keywords: Heavy Metals; Water contamination; Microfluidic device; Detection devices;

Electrochemical detection.

Table of content:
1. Introduction
2. Water analysis
3. Detection mechanisms
3.1 Electrochemical
3.2 Colorimetric
3.3 Fluorescence
3.4 Photoelectrochemical
3.5 Optical
4. Fabrication methods
 4.1 Wax printing
4.2 Inkjet printing
4.3 Laser-based
4.4 Screen printing
4.5 Xurography
4.6 Centrifugal microfluidics
5. Microfluidic devices for detection of water contaminants
5.1 Heavy metals
5.2 Pharmaceutical and biological entities
5.3 Nitrite, nitrate and nutrients
5.4 Organic contaminates and pesticides
5.5 Dissolved oxygen content and pH content
6. Conclusion and future perspective

1. Introduction
In the recent past, quick expansion of the global economy and technological progress have caused
increased environmental concerns [1]. Notably, the destiny of the aquatic environment has become a
serious concern worldwide. Around 97% of the earth’s water cannot be used as drinking water directly
because of its high salinity [2]. On the other hand, the water available for drinking purposes is being
heavily affected by the population growth, urbanization, and industrialization in most countries on the
earth. Water contamination has adverse effects on public health, which causes approximately 14,000
deaths per day globally [3]. The primary source for the water contamination is non-regulated and
unauthorized disposal of organic and inorganic wastes on the surface water from industrial and domestic
discards. These point-sources attribute to the addition of dangerous substances, including heavy metals,
nutrients, and pathogens to the surface water [4]. Additionally, non-point sources such as agricultural
waste, industrial and sewage water plants waste, land runoff from rainfall or snowmelt, and leaks from
buried landfills aid substantially to the water pollution. Heavy metals (e.g., arsenic (As), Cadmium (Cd),
and Lead (Pb), to name a few, naturally exist in the environment, including the aquatic environment, and
are essential for the functioning of the human body when present in an allowable concentration. A
concentration of heavy metals higher than the safe limit may cause a severe effect on public health due
to their mutagenic or carcinogenic attributes[5]–[7]. For example, many people in several districts of West
Bengal, India, suffer from keratosis, pigmentation, and chronic cough due to high concentrations of
arsenic in the ground water (~50 µg/L versus the safe limit of 10 µg/L for As) [8]. Nutrient contaminations,
such as nitrate and phosphorous, cause algae to grow faster than the ecosystem can handle, whereas
organic wastes lead to the blooming of pathogenic bacteria, viruses, protozoa, and worms harmful to
human health [9]. Adverse effects of these pollutants on human health are discussed in a later section.
The harmful impact of water contamination is unprecedented, both on human health and environmental
balance. Therefore, periodic monitoring of water quality is of extreme importance. Current state-of-the-
art techniques available for water quality monitoring include atomic absorption spectroscopy (AAS) [10],
electrochemical methods, inductively coupled plasma mass spectrometry (ICP-MS) [11], electrothermal
atomic absorption spectrometry (ETAAS) [12], flame atomic absorption spectrometry (FAAS) [13] and
many more. Even though these techniques are selective and sensitive, they require skilled labor and
expensive machine setup. Most importantly, they are not field-effective due to their non-portability and
sophisticated infrastructure. Therefore, there is a need for an alternative, which is reliable, highly sensitive
and selective, portable, user-friendly, cost-effective, and field-effective. Microfluidic devices have
emerged as supreme alternative, checking all these points for point-of-care applications [14]–[17].
Although microfluidics had emerged as a technique that heavily relied on silicon-based processes (e.g.,
lithography and etching), the emergence of several alternate microfabrication processes such as
xurography, inkjet printing, injecting molding, and 3D printing has opened up several options for
microfluidic devices with novel materials including papers, thermoplastics and polymers [18]–[21]. These
techniques also allowed for the easy integration of innovative sensing and detection units essential for
water quality monitoring.

This paper reviews the emerging trend of microfluidic devices for water quality monitoring. We first
discuss the adverse effect of water contaminants on human health to emphasize the importance of
regular water quality monitoring. Different detection methods are summarized depending on signal
transduction mechanisms used in the microfluidic devices for water quality monitoring. We further
discuss the fabrication processes employed to achieve microfluidic devices. Finally, we highlight different
microfluidic devices investigated for the detection of water contaminants. Figure 1 ellucidates on the
general information regarding substrates, fabrication processes and detection approaches explored to
develop microfluidic devices.

Microfluidic
Device

Target Analysis

Paper

Figure 1-Schematic representation of Microfluidic device

2. Water Analysis
Water quality has been majorly assessed by certain quality factors, including the absorption of nutrients,
concentration of heavy metals, pharmaceuticals, and organic contaminants (e.g., pesticides), pH and
dissolved oxygen content, and microorganism count [22]–[24]. Such factors should be under a permissible
limit in a water body. Beyond the permissible limit, the excess contaminants start affecting human health
as well as aquatic ecology. Below, we briefly describe the adverse effect of common water contaminants.
Table 1 has detailed the effects of the common water pollutants on human health, which also includes
the maximum permissible limit of the contaminants and typical sources of the pollutants.

2.1 Significance of heavy metals in water

Metals, featuring a density higher than 5 g/cm3, are called heavy metals [25]. Heavy metals are the most
common water contaminants. The most common heavy metals found in wastewater include copper (Cu),
arsenic (As), lead (Pb), chromium (Cr), cadmium (Cd), nickel (Ni), Iron (Fe), Gold (Au), cobalt (Co) and zinc
(Zn). These metals can emanate from anthropogenic activities or natural resources. Different natural
sources such as forest fire, volcanic eruption, biogenic sources, and wind-born particles leave heavy
metals in different forms in different environmental compartments (soil, air, and water). The
anthropogenic sources contributing to the heavy metal contaminations include agricultural waste (e.g.,
fertilizer, herbicides, and insecticide), industrial waste (e.g., electroplating, automobile, pharmaceutical,
and paint), domestic waste, mining, and manufacturing operations [26], [27]. The presence of heavy
metals beyond a permissible limit has an adverse effect on aquatic fauna and flora. In the case of food
chain systems, they will eventually result in food chemical contamination which can lead to various
diseases, threatening public health [28]. We discuss the health risks imposed by the commonly found
heavy metal contaminants in the following paragraphs. Furthermore, to provide an overview, we present
Table 1, which summarizes the heavy metal ions sources, their effect on human health, and their
permissible limit in drinking water, certified by World Health Organization (WHO).

Arsenic (As) is a highly toxic element to human health, which contaminates the drinking water primarily
through industrial waste or agrochemical waste [29]. Prolonged exposure of As to the human body affects
multiple organ systems in the human body, such as liver, bladder, lungs, and skin. International agency
for research on cancer (IARC) has classified arsenic compounds as Group 2B (organic) and Group 1
(inorganic) carcinogenic materials for human health [30]. Prolonged exposure to As increases the risk of
kidney, lung, and bladder cancer. Furthermore, excessive ingestion of As may cause acute intoxication to
the gastrointestinal systems, which may affect the cardiovascular system and central nervous system, and
therefore induce untimely demise. Other health diseases caused by chronic arsenic exposure through
drinking water include dyspepsia, peripheral neuropathy, Blackfoot disease, pigmentation and keratosis,
anemia, leucopenia, and thrombocytopenia [8].

Mercury (Hg) is discharged into the environment through different sources such as pharmaceuticals
industry, paper industry, horticulture industry, and chlorine and acidic soft drink production industry [31].
Both inorganic and organic forms of Hg in water are toxic for human health. Organic cpmpound
methylmercury readily accumulates in the food chain. It further crosses the blood-brain barrier upon
human digestion and attacks the nervous system, causing several health issues, including impairing
hearing and speech, restriction of muscle movement, and deterioration of skin and mucous membrane
[32]. Hg (II) ions in inorganic compounds are the precursor for methylmercury in the aquatic food chain.
Direct ingestion of Hg(II) ions primarily leads to accumulation in the kidney proximal tubule cells and
causes acute kidney diseases [33].

Apart from industrial activities and chemical pollution, lead (Pb) contamination in drinking water is
commonly caused by plumbing materials that contain lead [34]. Particularly, region where the water has
higher acidity and low mineral content, can corrode the plumbing materials releasing Pb in the drinking
water. Inorganic compounds of Pb is considered as possible human carcinogenic. Children, infants, and
fetuses are particularly vulnarble to Pb, even at low exposure levels. It dramatically affects the central and
peripheral nervous systems, which causes health issues such as learning disabilities, hearing impairment,
and blood cell functioning. The health issues developed within adults due to excess Pb exposure include
hypertension, obesity, kidney failure, and reproductive problems [33]. Cadmium (Cd) is found naturally in
ores and is frequently used in various industries such as nuclear reactors, electroplating industry, solar
cell industry, plastic stabilizers, battery industries, etc. According to WHO, maximum concentration of Cd
in drinkable water must be below 0.003 mg/L. Similar to Pb, Cd is also commonly released to drinking
water by corrosion of some galvanized plumbing and main water pipe materials. It can pose e an immense
threat to human health, as it has a long half-life (10-33 years) in the human body. The health risks
developed due to long-term Cd exposure include renal damage, disruption in calcium metabolism,
prostate cancer, and lung cancer[35]. One of the most worrisome cases was “Itai-Itai”, which affected
many citizens of Toyama Prefecture, Japan, due to mass exposure of Cd [36].

Table 1-Contaminants and their potential effects on human health

Contaminants Maximum Disease Sources References

contaminant
level (mg/L)
Arsenic 0.01-0.05 Skin cancer, effect on Geothermal activity, [37][38]
central nervous system, industrial and electronic [39]
cardiovascular, wastes, Agricultural [40]
dermatologic, application, pesticides,
immunologic, brown fertilizers, release of
pigmentation, hyper- untreated effluents,
pigmentation. Wooden electricity
poles.
Mercury 0.01-0.02 Internal cancer, effect on Natural deposits, coal [41]
immune system, combustion, agricultural [42], [43]
digestive system, Damage and industrial
to Neurobehavioral, applications, Volcanic
diarrhea, acrodynia, skin emission, paper and
rashes, asthma, etc. pulp preservatives,
municipal solid waste.
Lead 0.01-0.05 Internal cancer, kidney Natural deposits, fossil [44]
damage, paralysis, fuel burning, mining, [45]
decrease intelligence, PVC pipes, lunch boxes,
 reduces bone growth, jewelry, lead batteries,
muscular weakness, and manufacturing
hemoprotein, weight process.
loss.
Cadmium 0.005-0.01 Pancreatic cancer, breast Smelting, mining, [46]
cancer, ranal toxicity, paints, plastic, synthetic [47]
hypertension, neuron- rubber, natural [48]
cell death, DNA damage, deposits, electroplated
[45]
weight loss, kidney parts, photovoltaic cell,
disease, fatigue, etc. tobacco smoking,
sewage disposable.
Nickel 0.02 Lung cancer, lung Volcanic eruption, [49]
disease, liver toxicity, sewage sludge, forest [50]
skin disease. wires, industrial
wastewater.
Chromium 0.05 Gastrointestinal cancer, In soil and rocks [51]
lung cancer, reproductive deposition, leather [52]
toxicity, low blood sugar, industry, chrome plating [53]
liver and kidney damage, industry, volcano
dermatological, skin eruption, sewage
ulcers. sludge, cement
production
Copper 1-1.5 Adreno-corticol Fertilizers, building [54]
hyperactivity, allergies, construction, electronic [55]
anemia, lung cancer, liver product, photovoltaic
and kidney damage, cell, tanning, machinery
alopecia, vomiting, and transmission
stomach cramps. industry.
Iron 0.2-0.3 Lung cancer, an Corroded iron pipeline, [56]
autoimmune disorder, natural deposits, water [57]
irritable bowel supply line.
syndrome,
gastrointestinal bleeding,
vomiting, and diarrhea.
Aluminum 0.1-0.2 Mouth ulcers, diarrhea, Industrial waste and [58]
skin rashes, vomiting and industrial applications [59]
nausea, arthritic pain.
Nitrate 45-50 Internal cancer, gastric Agricultural usage, [60]
problems, blue-baby sewage sludge, septic [46]
syndrome, Parkinson’s tanks, animal waste.
disease
Nitrite 0.2 Blue baby syndrome, Agricultural usage, [61][62][63]
gastric problem septic tanks, natural
 deposits, sewage
sludge, animal waste.
Pesticide 1,3- 0.02 Carcinogenic cancer, Agricultural applications [64]
dichloroprop- brain tumors, skin
ene irritations.

2.2 Pollution by biological contaminants

Biological contamination of water, which typically arises from impure water and poor hygienic practices,
is caused by living microorganisms, such as viruses, bacteria, fungi, protozoa, and algae. Environmental
Protection Agency (EPA) of the United States has found that more than 500 waterborne (enteric)
pathogens are available in drinking water [65]. These waterborne pathogens have a staggering impact on
human health. For example, waterborne pathogenic microbes such as Vibriocholera, Salmonella, and
Escherichia Coli cause sicknesses such as cholera, typhoid, and gastrointestinal problems [66], [67].

Pharmaceutical wastes play a significant role in boosting biological contamination. These wastes mainly
originate from the medicine manufacturing industry, hospitals, and clinical laboratories, and include
drugs, antibiotics, steroids, hormones, and analgesics [68]. These chemical substances often alter the pH,
temperature, oxygen level, and nutrient concentration of the aquatic environment, which may boost the
growth of biological contaminants. Furthermore, wastes such as contaminated syringe, needles, surgical
blades, and infected biological samples directly introduce biological contaminants in the surface water,
which can later directly or indirectly affect the human health.

2.3 Contamination by Nitrite, Nitrate, and Nutrients

Nutrient elements, mainly nitrogen (N) and phosphorus (P), are essential for all living organisms. Excessive
nutrients leads to faster growth of algae, which can be overwhelming to the ecosystem. Algal blooms in
aquatic habitats can lead to a severe reduction in oxygen level, which directly affects aquatic biodiversity
[69]. Furthermore, the algal bloom may cause bacterial growth and release toxic substances in water,
which are harmful for human health. Nitrates and nitrites do not volatilize and have a high potential to
migrate in groundwater due to their high-water solubility and weak retention by soils. The presence of
nitrates in ground water is troublesome in those places where ground water is the primary source of
drinking water. Furthermore, the nitrates that remain in the water are also consumed by plants and other
organisms [70], which may aid to the nitrate ingestion of humans. A high level of nitrate ingestion is
particularly harmful to infants, as serious health problems arisedue to lack of oxygen in the drinking water.
For example, methemoglobinemia or “blue baby syndrome” is often linked to nitrate contamination,
which is one of the major diseases for infants in many places in the United States[71].

3. Detection mechanisms employed in microfluidic devices for the water quality

monitoring
Several detection mechanisms have been explored over the years for microfluidics-based water quality
monitoring systems. Among different mechanisms, the most popularly used methods include
electrochemical detection, fluorescence detection, and photoelectrochemical detection. Other detection
mechanisms include colorimetric, chemiluminescence, absorbance based, surface plasmon resonance,
quartz crystal microbalance, etc. Due to high popularity in the microfluidics community, we only discuss
the mechanisms of electrochemical detection, photoelectrochemical, fluorescence, and colorimetric
detection in the following subsections.

3.1 Electrochemical detection

Electrochemical analysis is a powerful detection method, which mainly relies on the electrochemical
interaction of an analyte on an electrode surface. The electrochemical interaction is primarily realized by
reduction-oxidation (redox) reactions, which can be measured by the electrical signals including current,
potential and charge. In water quality monitoring, the presence of water contaminations is realized
through changes in the electrical response influenced by the contaminants. Electrochemical detection has
been widely explored for on-chip and real-time monitoring systems due to their simple manipulation,
inexpensive analysis, ease of portability, high sensitivity, and selectivity [72]. The detection process is
typically performed in a three-electrode electrochemical cell consisting of a working electrode, a
reference electrode, and a counter electrode. The fabrication steps of electrochemical sensors are shown
in figure 2. The performance of the electrochemical detector is often tuned by modifying the working
electrode, upon which the redox reactions occur. Miniaturization of electrodes through microfabrication
processes has allowed the integration ofthree-electrode electrochemical detection systems within a
microfluidic channel without compromising the performance of the detection method. Several
electroanalytical methods have been studied within a microfluidic system, among which the most popular
ones are amperometry, voltammetry, conductometry, and potentiometry [73].

In voltammetry, the potential between the working electrode and the reference electrode is varied over
time, and the current response is measured over the potential change. A current versus voltage graph is
obtained through this process. The peaks obtained in this graph represent the redox reactions that occur
on the working electrode. The peaks are identified and quantified to analyze the presence of the analyte.
Voltammetry allows to quantify multiple analytes simultaneously, if the analytes yield different redox
potentials. Various forms of voltammetry measurements are used for electrochemical analysis, which
includes cyclic voltammetry (CV), linear sweep voltammetry (LSV), square wave voltammetry (SWV), and
stripping voltammetry (SV). In contrast to voltammetric measurement, amperometric measurement
involves the measurement of current at a constant voltage, and the current is recorded as a function of
time [74]. The operating voltage is determined where a maximum redox activity is quantified.
Electrochemical detection based on conductometry is a universal method for ion detection. It is a general
method commonly used two-electrode system for measurement of electroactive compounds [75].
Potentiometry sensors measure the potential difference between indicator electrode and counter
electrode in a two-electrode system. Potentiometry is used to measure the activity of most electroactive
components with the help of the Nernst equation. This process is susceptible; broad response range, short
processing time, rapidity, and reproducibility make them suitable for detecting heavy metal ions [76].
 Figure 2 - Schamatic of fabrication steps of a paper-based electrochemical sensors (a) A pattern for the
testing area is drawn and wax-printed. (b) Electrodes are screen-printed and thermally cured [77].

3.2 Photoelectrochemical detection

Photoelectrochemical (PEC) sensing is an essential branch of electrochemical detection, which recently

has witnessed rapid development. The PEC sensor is a more sensitive technique, simple instrumentation,
low-cost, high selectivity, and detecting all kinds of analytes [78][79]. Figure 3 depicts a general illustration
and the working principle of PEC devices. An irradiation source, a monochromator, an electrochemical
workstation, electrodes, and finally a data acquisition system are all part of the PEC system. Working
electrode (WE), counter electrode (CE), and reference electrode (RE) comprise a three-electrode system
(RE). The working electrode material must be semiconductor so that when photons with higher energy
absorb on the photoactive surface, an electron-hole pair is formed . Following that, the photogenerated
charge carrier (electron-hole) participates in the redox reaction and produce an electrical signal in the
electrolyte solution.

.
 i on
Monochromator
off t
Electrochemical
workstation
Light source Signal acquisition

Beam splitter

Reduction/Oxidation
e-

Reference electrode

Working electrode
Excitation filter CB

Counter electrode
VB
h+
Mirror

Figure 3 - Schematic of working principal of photoelectrochemical sensors

3.3 Fluorescence detection

Fluorescence is also one of the popular optical detection techniques used for water contamination
detection and monitoring. It absorbs light at a specific wavelength and emits light at a longer wavelength;
the instrument includes a light source, filters, a focusing lense, and a detector, as shown in the figure 4.
Excitation, excited-state lifespan, and fluorescence emission are the three phases of the fluorescent
detection process. To induce luminescence of the fluorophores, a source of light of an appropriate
wavelength is used in the processing stage. The consequent light is screened to separate the emission
photons from the excitation photons, and the intensity of the emission photons is quantified and used as
an indicator of the concentration of the target analyte [80]. The difficulty of probing flow and mass
transport in microsystems due to structural constraints is one of the many barriers in microfluidic design
and development. Fluorescence technique, when combined with microfluidic devices, can be used to
investigate flow profiles and determine flow rate, and also analyze diffusion-based motion and measure
the diffusion coefficient in the absence of flow [81].In fluorescence measurement, the analyte signal is a
function of analyte concentration and intensity of incident excitation radiation. To detect heavy metal
ions, receptors should be used as a chelating agent for efficient interaction with analytes. Fluorescent
sensors employed with energy transfer processes or electron transfer process for the detection of heavy
metal ions. Fluorescent microfluidic devices based on energy transfer process are förster resonance
energy transfer (FRET), nanometal surface energy transfer (NSET), chemiluminescent resonant energy
transfer (CRET). Techniques based on electron transfer are interfacial electron transfer (IET),
intramolecular photoinduced electron transfer (IPET).
 Excitation light

Filtration

Microchannel

Focusing and Photon Data processing

filtration detection and output

Figure 4 - Schamatic of fluorescence detection setup with a microfluidic device

3.4 Colorimetric detection

Colorimetry integrated with microflμidic devices, particularly with paper-based devices, is broadly used
as the most suitable detection technique due to its simplicity, compatibility with relatively low-cost
reporting systems, visual readouts, superior stability, and feasibility to operate in remote areas. Figure 5
represents the steps involved in the colorimetric detection technique for contaminants in wastewater.
Colorimetric detection relies on the change of color in the presence of the targeted analyte. The color
change is actuated by a chemical reaction between the analyte and a reaction agent. The reaction agents,
which include an enzymatic assay, a redox indicator, pH indicators, and nanoparticles (gold, silver, and
carbon dots), are responsible for the generation of color on paper [82]. In some cases, the reaction does
not result in a change of color. Instead, it causes a change in the pH or redox behavior. A redox or pH
indicator is used in these cases, which shows a change of color due to the chemical stimulus [73]. Color
homogeneity is an important parameter for colorimetric readouts in microfluidic devices since it allows
for better measurements with greater figures of merit of the analytical method. Some parameters
influence readouts homogeneity, such as device design, assay implementation, digitalization and data
processing selection, and substrate modifications. An optical system typically records the color change for
further analysis.
 Hydrophobic Cell phone
barrier cameras

Scanners

Image
digitization

Hand held
Sample Introduction Colorimetric readouts
readers

RGB
model
HSV
model

Data
handling Image Automated
analysis analysis software

CIE Computer vision

model based analytical

Figure 5 – Steps involved in colorimetric detection in contaminated water sample

4. Fabrication of microfluidic devices used for water contamination detection

The fabrication of μPADs is mainly based on the making of hydrophilic zones on paper, patterned by
hydrophobic or physical barriers using different hydrophobic agents or cutting methods, individually [83].
Numerous ways have been stated to fabricate the µPADs, such as photolithography, inkjet etching, plasma
treatment, paper cutting, wax printing, inkjet printing, hot embossing, laser treatment, screen printing,
and many more. The most popular method for fabricating microfluidic channels in thermoplastic materials
is hot embossing, photolithographic processes [84]. Double-sided tapes are developed for the fabrication
of microfluidic channels, which is a cheap, reliable, and rapid method for highly uniform cross-sectional
dimensions and proper adhesion in hybrid systems. Early microfluidic devices were generally built using
silicon substrate; nowadays even transparent polymers, glass, metals, and ceramics too used for
microfluidics devices. Microfluidic devices are generally made by combining two layers: a substrate layer
(micro/nano structured) and a channel layer (microchannel impression).
4.1 Soft Lithography

Soft lithography is a fabrication technique where micro/nano structures are replicated on an elastomer
using a patterned mold. Polydimethylsiloxine (PDMS) is the most popular elastomer used for the
fabrication of microfluidic devices using soft lithography due to its versatile properties such as low cost,
non-toxicity, chemical inertness, biocompatibility, mechanical flexibility and durability [85]. The process
flow for soft lithography is schematically shown in Figure 6. The process starts with the fabrication of the
mold. Typically photolithography is one of the popular methods to fabricate the mold for microfluidic
devices. Generally, the photolithographic process includes a series of steps such as photomask creation,
wafer cleaning, photoresist application, UV exposure, and development of substrate. In next step after
creating master mold with the help of photolithographic technique, an elastomeric material typically
PDMS, is cast against a master mold and replicated the features over it. Many researcher reported
microfluidic devices fabrication using micro-replication double inversion technique [86]–[88].

UV light

Photoresist

Mask

Substrate Photoresist UV exposure & Master device

development

Glass cover PDMS

Polymer
removal

UV assisted Embossed Polymer

bonding channel casting

Figure 6 - Schamatic illustration steps involved in soft lithography

4.2 Paper-based Analytical Microdevices (µPADs)

Paper-based analytical microdevices (µPADs) are an emerging platform for environmental, biomedical,
and point-of-care (PoC) analysis. µPADs have countless attractive properties such as inexpensive,
biocompatible, biodegradable, and small in size. The fabrication of μPADs is mainly based on the making
of hydrophilic zones on paper, patterned by hydrophobic or physical barriers using different hydrophobic
agents or cutting methods, individually [83]. Numerous ways have been stated to fabricate the µPADs,
such as photolithography, inkjet etching, plasma treatment, paper cutting, wax printing, inkjet printing,
hot embossing, laser treatment, and screen printing, to name a few.

Fabrication
Technique

Soft
µPADs Xurography
Lithography

Wax printing Inkjet printing Laser based Screen printed

Figure 7- Schematic of different fabrication techniques for paper-based microfluidic device

4.2.1. Wax Printing

Wax has the advantages of easy accessibility, ultra-low-cost, non-toxicity, and ease of processing with
heat. Wax is one of the most commonly used materials to form hydrophobic barriers in cellulose fiber.
Wax 3D printer is a new approach for fabricating microfluidic devices, enabling rapid prototyping of
complex structures, fast processing, avoiding solid-to-solid bonding by introducing dummy structures to
support the main parts. Figure 8 presented the workflow of steps from the device's design to the casting
of the microfluidic channels via the wax 3D printing method.
 (i) CAD drawing (ii) Wax printing (iii) Support
material removal

(vi) Final geometry (v) Wax removal (iv) PDMS casting

Figure 8 - Schamatic of flow chart of wax printing

Zhang et al. proposed a paper-based microfluidic device using laser-induced selective thermal reflow for
wax penetration. In this fabrication technique, they have applied a layer of wax on a filter paper, and then
a low-cost diode laser (as shown in figure 9) was allowed to scan the designed area of the backside of the
filter paper. Due to laser irradiation, wax was heated and melted down and penetrated through the filter
paper, and form hydrophobic barriers. This patterned barrier on filter paper defines a flow path for fluidic
samples [89].

Figure 9- Fabrication procedure for laser-based microfluidics: (a) blank filter paper; (b) an evenly
distributed wax layer; (c) laser scan on the backside of the filter paper; (d) the wax penetrated through
the whole thickness[89]

Similarly, Chen et al. fabricated flexible and straightforward three-dimensional nanofiber-based

microfluidic analysis devices (3D-µNMADs) for water quality testing. Nanofiber membranes and
hydrophobic wax barriers are printed alternately to build 3D-µNMADs. The 3D-µNMADs show significant
promise for rapid and flexible environmental monitoring, especially in resources-limited regions [61].

4.2.2. Inkjet Printing technique

Inkjet printing is a new fabrication technique for paper-based microfluidic devices. It can deliver
biomolecules and indicator reagents with precision into the microfluidic patterns to form
biological/chemical sensing zones [90]. Inkjet printer performs on a fundamental principle, contactless
spreading of very small-sized (picoliter-sized) droplets of liquids (ink) onto a pre-defined position of a
substrate to generate microchannels. The main advantages of inkjet printing are high speed, high volume,
and low-cost commercial printing technology, facile design adaptability, deposition of a large variety of
materials from the liquid phase, and relatively high lateral resolution. Inkjet printing has become an
essential tool in the industry for mass production and printed electronics in chemistry [91], biology, life
sciences and used for the fabrication of DNA chips[92].

Abe et al. developed a device using an inkjet printing method to fabricate microfluidic multianalyte
chemical sensing devices and a patterned paper. They fabricated three-dimensional hydrophilic
microfluidic patterns, flow channels around 550-μmwide, and sensing area 1.5mm*1.5 mm using an inkjet
printing on a filter paper. In this approach, the paper substrate is first soaked into a polystyrene solution
(1.0 wt% in toluene) to convert it into an entirely hydrophobic material and drying at room temperature
for two hours. Then the hydrophobic paper is exposed to the inkjet printing of picolitre volumes of toluene
and sensing inks as illustrated in figure 10 [93].

Figure 10- Schematic representation of the fabrication process of the inkjet-printed microfluidic
multianalyte chemical sensing paper featuring microfluidic channels [93]

4.2.3. Laser-Based Fabrication Approach

The laser-based direct writing (LDW) technique is used to create fluidic patterns on the substrate using
the concept of light-induced photopolymerization. LDW approach is noncontact, and it eliminates the
requirement of expensive masks, clean room-based steps, and custom-designed types of equipment.
LDW is advantageous for the fabrication of biological and biomedical devices because it minimizes any
chance of cross-contamination. The minimum width for the hydrophobic barriers that prevent fluid
leakage was found to be 120 μm in a conducted study, sones et al. fabricated laser-based device has a
fluidic channel with barrier wall width up to 80 μm [94], He et al. fabricated a microfluidic device in
nitrocellulose with a lateral dimension of 100 μm and channel wall dimensions of 60 μm [95]. Kant et al.
utilized CO2 laser for micromachining of Polymethylmethacrylate (PMMA) devices and optimize
dimension precision and surface roughness. They discussed about the effect of process parameters such
as laser power, print resolution, raster speed, etc., quality of microchannel surface examined by using 3D-
profilometry and Field emission scanning electron microscope (FESEM). It is observed that optimum
surface roughness of this process is around 7.1 μm achieved at the optimum value of the process
parameters like raster speed 7.5 mm/s, laser power 17.9 W, and resolution 1200 DPI (dots per inch)
[96][97].

4.2.4. Screen Printed Technique

Screen printing is a customary printing technique including a customized mesh and used to move pattern
onto a substrate, a squeeze or flat object is used for material (ink) is transferred selectively through a
mesh and making some areas impermeable. It is inexpensive, and simple technique, which provides high
resolution and repeatability, rapid fabrication for mass production, less instrumentation and materials
required. Sameenoiet al. presented a polymer-based screen-printed PADs, in which patterned screen and
polystyrene dissolved in toluene was used for printing. In this technique, they deposited a polystyrene
solution onto the patterned screen placed over the paper as showed in figure 11. The polystyrene solution
passes through the screen and paper, after the evaporation of the solvent, hydrophobic barrier remains,
which provides high channel fidelity [98].

Figure 11-Schematic of the one-step polymer screen-printing method for patterning the hydrophobic
barrier on the paper using a polystyrene solution and a patterned screen[98].
Wax screen-printed device can be fabricated by simply using two steps, printing patterns of solid wax on
the surface of paper using a simple screen-printing method and using a hot plate to melt the wax into
paper to form complete hydrophobic barriers. Wax screen-printing is cheaper than wax printing because
it requires only an inexpensive screen and a hotplate[99].

4.3. Xurography

Xurography arises from the Greek word that combines two words ‘xuron’ and ‘graphe’ means razor and
writing, respectively. As the name suggests, xurography is a technique for patterning sheets using a blade.
In the recent years, xurography has emerged as an inexpensive, simple and quick microfabrication
technique for the fabrication of 2D and 3D microfluidic devices [100]. Xurography is firstly introduced by
Bartholomeusz, they used this technique for creating microfeatures on various films (thick and thin
polymer film, hard and soft film) of 6 µm width and 25 µm thickness. Three type of cutting method drag
knife, true tangential, and emulated tangential with different blade angle orientation 30°, 45°and 60° were
used to create positive and negative structure [101]. In a typical fabrication process, microfluidic channels
are designed using a CAD software and later used to pattern a polymer or/and a double-sided pressure-
sensitive adhesive (PSA) film using a cutting plotter machine. The patterned polymer or/and PSA films are
aligned and assembled with a substrate and a cover layer of polymer to complete the microfluidic device.
Lowest dimension achieved using this technology is ~200 µm [102] .

4.4. Centrifugal microfluidics

Microfluidic devices basically operate on two kinds of platform either Lab-on-Chip (LoC) or Lab-on-Disc
(LoD) platform. In LoC platform external micropumps are required to flow the liquid through microchannel
but in LoD platform centrifugal forces are the primary driving force to move liquid through the
channels[103]. Centrifugal microfluidic rotating platform utilize Capillary, Coriolis, Euler and centrifugal
forces to transport and manipulate liquids. These devices require no external pumping for fluid
movements. They offer number of advantages over LoC devices such as, ease of multiplexing, particle
handling, actuation forces can easily scale, independent of physiochemical property of fluid (pH, viscosity),
not require high voltage power source. Centrifugal platforms are widely used for environment monitoring
(air, land and water), and biomedical application (cell separation, DNA microarray) [104], [105].

5. Microfluidic devices for detection of water contamination

5.1 Microfluidic devices for heavy metal detection

Mercury is among the most hazardous heavy metals on human health. Many types of microfluidic devices
and μPADs have been reported previously for the detection of Hg(II) in different types of waters like
drinking water, water from pond and river, and wastewater from industries [106].

Pourreza et al. developed paper-based analytical devices (PADs) for monitoring Mercury (Hg2+)
concentration with the employ of curcumin nanoparticles (CURNs). The paper-based probe was created
by using the wax dipping technique and adding CURNs as the sensing reagent. The device has calibration
graph was linear in the range of 0.5–20 μg mL−1 of Hg2+ with the limit of detection(LoD) of 0.17 μg mL−1
(without preconcentration) and 0.01–0.4 μg mL−1 of Hg2+ with the limit of detection of 0.003 μg mL−1 (after
50 times preconcentration) [107].

Meelapsom et al. developed a chromatic analysis based on a simple red green blue (RGB) color model for
sensitive and selective determination of mercury (II) by monitoring the color change of a microfluidic
Paper-based analytical device (µPAD). The device was fabricated by using alkyl ketene dimer (AKD)-inkjet
printing and doped with unmodified silver nanoparticles (AgNPs) and color intensity was detected by using
a digital camera. The developed system enabled quantification of mercury (II) at low concentration with
the detection limit of 0.001 mg L−1 and small sample volume uptake (2 µL)[108]. Wu et al. presented a
work in which he used polystyrene–divinylbenzene (PS-DVB) microspheres for heavy metal ions detection,
PAN was immobilized on a wax-printed filter paper to establish colorimetric copper (II) ion detector.
Concentration of copper (II) ion can be noticed by a color change from orange to red corresponding (from
the figure 12 (a)) to the by adding eluent obtained from the pre-separation process. The whole process
can be finished within 3 min and the limit of detection (LOD) for copper (II) ion was calculated as 0.340 μm
[109]. Li et al. fabricated a simple double-layered three-dimensional (3D) microfluidic paper-based
analytical device (μPAD) which can detect six metal ions—Fe(III), Ni(II), Cr(VI), Cu(II), Al(III), and Zn(II)
simultaneously. The 3D μPAD device as described in figure 12 (b), has two paper layers a top layer is the
pretreatment layer and a bottom layer is colorimetric detection layer. The detection limits recorded as
low as 0.2, 0.3, 0.1, 0.03, 0.08, and 0.04 mg/L for Fe(III), Ni(II), Cr(VI), Cu(II), Al(III), and Zn(II)
respectively[110].
Figure 12-(a) Fabrication technique and detection schematic for Cu (II) ion with colorimetric scheme[109]
(b) Fabrication of the double-layered three-dimensional microfluidic paper-based analytical device (3D
μPAD) for multiplexed colorimetric detection of six metal ions[110]. (c) Resolution testing of μPADs made
by the atom stamp printing (ASP) method. (i) Structural picture of the hydrophilic channels. (ii) Structural
picture of the hydrophobic barriers. (iii) Hydrophilic channels tested with blue dye. (iv) Hydrophobic
barriers tested[111]. (d) Schematic representation of microfluidics-assisted SERS sensor (i) The Ag
nanostructures were obtained inside the microfluidic channel via electroless galvanic replacement
reaction. (ii) Washing by ethanol (iii) The probing molecules were introduced (iv) Raman microscope used
for SERS detection[112].

Surface-enhanced Raman spectroscopy (SERS) is a highly sensitive technique to detect targets on the
single-molecule level on the surface with noble metal (e.g., Au, Ag, and Cu) nanostructures; SERS spectra
of molecules are stronger 1010 to 1011 times over Raman signals. On-chip fabrication of surface-enhanced
raman spectroscopy (SERS)- active materials enables continuous, real-time sensing of targets in the
microfluidic chip, it is faster than conventional methods the whole reaction could be achieved by less than
10 mins, while the traditional methods take hours. Yan et al. [112] present a novel method using a
microfluidic channel via a one-step electroless galvanic replacement reaction for the synthesis of Ag
nanostructures. Figure 12 (d) show the SERS assisted microfluidic device and detection principle. The
microfluidic channel has a Cu base, which can reduce Ag ions to Ag nanoparticles in the presence of an
AgNO3 solution. They perform two experiments to verify the utilization of SERS substrate, first, one to
detect Hg (II) ions in aqueous solution using microfluidic assisted SERS sensors and second, they coupled
SERS-active material with a concentration gradient generator for continuous SERS detection. The limit of
detection (LoD) of this microfluidics assisted SERS sensor was reached up to 1 × 10−7 M for Ag and Hg (II).

Table 3 concise the various heavy metal found in the contaminated water and their mode of detection,
limit of detection and fabrication techniques of microfluidic device is discussed.

Table 2- Heavy metal ions and their detection scheme with microfluidic devices

Heavy Mode of Substrate Fabrication Limit of Reference

Metal detection Method Detection s
Cd (II), Pb (II) Electrochemical Paper Lithography 1.2, and 1.8 µg L-1, [113]
respectively
Cd (II), Pb (II) Electrochemical ABS 3D printing 0.5, 0.2 µg L-1, [114]
respectively
As (III) Electrochemical Microchip Readily 0.8 ppb [115]
available
Sn (II), Pb (II) Electrochemical Whatman paper Wax printing 0.26, and 0.44 ng [116]
mL-1
Hg(II), Ag (I) Fluorescence Paper Physical 87 to 116% for [117]
absorption Hg2+, and 91% to
126% for Ag.
HG (II) Fluorescence Silicon wafer Soft 85% to 103% [118]
lithography
Cu (II), Hg (II) Fluorescence Whatman paper Wax inkjet 0.035 and 0.056 [119]
printer µg L-1,
respectively
Cu (II) Fluorescence Glass fiber Surface 0.012 mg L-1 [120]
paper imprinting
Cu(II),, Ni(II), Colorimetric Paper Wax printing 0.29, 0.33, 0.19, [121]
Cd (II), Cr(VI) 0.35 ppm
respectively

As (III) Colorimetric paper Mico 1.0 ppb [122]

machining
method

Ni (II), Cr (VI), Colorimetric Patterned Condensation 0.24, 0.18, 0.19 [123]

Hg (II) chromatograph reaction ppm respectively
y paper
 Cu (II) Colorimetric Whatman #2 Laser jet 1.7 mg L-1 (in [124]
filter paper presence of
chrome azurol S),
(in presence of
pyrocatechol
violet)1.9 mg L-1
As (III), As Colorimetric Polymer, plastic Vacuum 5-20 µg L-1 [125]
(IV) forming

Cu (II) Colorimetric Paper Atom stamp 1 mg L-1 [126]

printing

Cu (II), Co Colorimetric Paper Wax printing 0.32, 0.59, 5.87, [127]

(II), Ni (II), Hg 0.20, and 0.11
(II), Mn (II) mg L−1,
respectively
NI (II), Cu (II) Colorimetric Whatman filter Wax printing 4.8, 1.6, 0.18 mg [128]
Cr (II), paper L−1, respectively

Pb (II) Colorimetric PDMS Photolithogra 10 µM [129]

phy
As (III) Atomic Whatman paper Wax printing 10 µg L-1 [130]
absorption
spectroscopy
Pb (II) Electrophoresis PDMS and glass Soft 0.44 ppm [131]
slide lithography

μPADs have rapidly advanced in recent years, Guan et al. fabricated a new type of μPADs by atom stamp
printing (ASP). This device is used to detect the different concentrations of cu2+ via the colorimetric
method and distance-based detection method and reduce the detection limit up to 1mg/L[111].
Resolution is an important parameter to evaluate the performance of μPADs. Resolution refers to the
minimum channel width of the fluid flow passages on the paper and the minimum width of the
hydrophobic barrier that prevents the flow of fluid. From figure 12 (c) (i) and (ii) we can oberve that the
designed structure of the hydrophilic channels size have 0.3 to 1.3 mm channel width and hydrophobic
barriers have width ranges from 0.2 to 1.1 mm. To observe the flow through the hydrophilic channels and
the hydrophobic barriers accurately, a blue dye was added to the channels. As shown in figure 7(c) (iii),
(iv), it was obvious that when the width of the hydrophilic channel was 0.4 mm, the liquid could flow
normally, and when the hydrophobic barrier was 0.2 mm, the flow was blocked.

5.2 Detection of Pharmaceuticals and biological entities

Pharmaceutical residues are regarded as a particularly dangerous type of emerging contaminant in water
in developing countries, whereas microfluidic devices for water analysis could provide a valuable ability
to detect those pollutant molecules in water. Bacteria-related waterborne diseases are one of the world's
most serious public health issues. Altintas et al. describe the successful design and fabrication of a novel
microfluidic-based electrochemical biosensor for the rapid detection of the waterborne pathogen E. coli.
Using the nanomaterial amplified immunosensor assay, a detection limit of 50 cfu mL -1 was achieved in
water samples [132].

Diclofenac (DCF) is recognized as an emerging contaminant due to its presence in surface waters and toxic
effects to aquatic organisms. Rama et al. developed a paper-based platform for detection of highly
sensitive DFC. They used electrochemical detection technique, plateform consist three electode system
where carbon-ink paper-based working electrode and gold plated metallic wire as counter and reference
electrode[133]. Drug development is a complicated process, and that involves several costly and time-
consuming steps and processes. Microfluidic chip technology offers great advantages in high-throughput
drug screening (HTDS) and has been accepted as an advantageous tool for cell biology research and the
most influential benefit of microfluidics for cell-based drug-testing assays is the ability to reconstitute the
cell microenvironment at the microscale [134]. Sun et al. have been used these microfluidic devices for
the extraction of compounds from biological media, they have been applied in the separations of organic
molecules, cells, and dyes [135]. Fatih et al. have presented a hand-held biosensing platform that
integrates a plasmonic detection modality with a microfluidic chip, detects hemoglobin—an iron carrying
protein in red blood cells. This miniaturized platform provides label-free detection, simple configuration
for user-interface, facile sampling, assay-time down to detection, and inexpensive disposable chips[136].

5.3 Detection Devices for Nitrite, Nitrate, and Nutrients

Memories al. introduced a pair of µPADs (shown in figure 13 (c)) with identical fluidic design for the
determination of nitrite and nitrate in environmental samples employ with the Griess reaction. One of the
µPADs is used for the detection of nitrite only and the other one allows the detection of both nitrite and
nitrate after the reduction of nitrate to nitrite in a hydrophilic channel containing Zn microparticles and
acting as a virtual flow-through solid-phase reactor. Inkjet printing method is used for fabrication of these
simple, low cost, environmentally friendly µPAD and limit of detection (LOD) for the optimal condition is
1.0 and 19 for nitrite and nitrate respectively [137].

In the similar strategy Thiago et al. developed a microfluidic paper-based analytical device (µPADs)
working on the principle of colorimetric detection for the determination of nitrite present in clinical, food,
and environmental samples. Figure 13 (a) shows µPADs having eight circular detection zones and one
central zone to sample inlet interconnected by microfluidic channels were fabricated by a simple and fast
stamping process. The modified Griess reaction was performed through the colorimetric determination
of nitrite. For good stability of the background calorimetric response device stored in absence of light for
12 hr, the analytical sensitivity and the limit of detection achieved were 0.56 (AU/µM) and 5.6 µM,
respectively[138].
Almeida et al. [139] developed a cheap, reusable, and highly selective microfluidic paper-based analytical
device (μPAD). Molecular ammonia and ammonium cation in wastewaters can be determined by using
it. Ink-jet printing was used to produce circular hydrophilic sample and reagent zones on the proposed
μPAD. The pattern was designed by using the drawing facility in Microsoft Office TM, and Whatman Grade
4 filter paper (0.205 mm thick) was used for printing and it was heated at 105oC for 30 min to make the
printed hydrophilic permanent pattern. The proposed μPAD card size was 78 mm x 58 mm and it
contained 15 pairs of circular hydrophilic sample and detection zones. μPAD was fabricated by
accumulating the following three layers, as shown schematically in Figure 13 (b): (1) a layer of patterned
filter paper containing a set of fifteen 7 mm in diameter hydrophilic sample zones (Zone 1); (2) a PTFE
hydrophobic microporous membrane layer (12 mm x 78 mm, 0.1 mm thickness); and (3) a sheet of
patterned filter paper holding a set of fifteen 3 mm in diameter hydrophilic detection zones (Zone 2).

Figure 13-(a) Schematic fabrication diagram of the proposed gas-diffusion μPAD, diameters of Zone1 and
Zone 2 are 7 and 3 mm, respectively [138]. (b) Membrane less gas separation microfluidic paper-based
analytical devices (MBL-GS μPADs)' for analysis of volatile and non-volatile compounds (device I & device
II), respectively[140]. (c) Schematic diagrams of the proposed 2D µPADs (b) 3D µPADs (c) a photographic
image of an individual unused 3D µPAD (d) a card incorporating 6 used 3D µPADs [137].

Phansi et al. present a new chemical sensing device called ‘membrane-less gas separation microfluidic
paper-based analytical devices’ (MBL-GS μPADs) for quantitative analysis of the volatile and non-volatile
compound. MBL-GS μPADs were designed to make the fabrication of the devices simple and user friendly
and available at a low cost. An MBL-GS μPAD consists of three layers: ‘donor layer’, ‘spacer layer’, and
‘acceptor layer’ as referred in figure 13 (b). The donor and acceptor layers are made of filter paper with a
printed pattern. The spacer layer is mounted between donor and acceptor layers with the help of two-
sided mounting tape, 0.8 mm thick, with a small disc cut out for the gas from the donor zone to diffuse to
the acceptor zone[140].

5.4 Organic Contaminants and Pesticides

Organic contaminants have various antagonistic health impacts because of their toxicological effects and
hazardous nature to human health. Sensors to detect volatile organic compounds (VOCs) got much
attention most of the fabrication of sensors involves complicated procedures; hence, µPAD-based sensors
have been accounted for VOCs’ recognition. Air, water, soil, food, and feed products are always
contaminated with insecticides or pesticides. Employing ingestion, inhalation, and dermal assimilation,
pesticide toxicity can happen and is related to neurotoxicity, hepatotoxicity, renal harmfulness,
dermatitis, and cancer. Microfluidic PADs offer cost-effective, practical methods for quickly examining
food items for pesticides. Chemical oxygen demand (COD) is one of the most significant parameters and
has been generally used to show the organic pollution in aqueous systems. Many researchers utilized
semiconducting nanomaterials coatings for photocatalytic based degradation of textile dyes [141]–[144].

Sicard et al. developed a combination of paper-based sensors and a novel smart-phone application for on-
site quantification of colorimetric readouts as an ultra-low-cost solution to monitoring water quality. The
system utilizes a paper-based analytical device (µPAD) for low-cost monitoring environmental
contaminants at a large-scale. It produces a colorimetric signal that is dependent on the concentration of
a specific target; a cell phone equipped with a camera for capturing images of two µPADs one tested with
a water sample and the other tested with clean water (ddH2O) that is used as a control; and an on-site
image processing app that uses a novel algorithm for quantifying color intensity and relating this to
contaminant concentration [145]. Figure 14 shows the sequence of steps used to develop paper sensor
to analyze water samples.
 (i)

(ii)

Figure 14- (i) Sequence of steps for using the paper sensor to analyze water samples (ii) Sequence of
detection of presticide using iphone 6 ios (A) Initial screen (B) Positioning of sample (c) Image of the strip
(D) Processing (E) Pixel count for the control (F) GPS coordinate for the location [145]

5.5 Dissolved Oxygen Content and pH Content

Microfluidic bioreactors, lab-on-chip [146], cell-on- chip [147] and organ-on-chip [148] devices are useful
tools enabling biomimetic microsystems. They provide key information of living human organs and
industrial fields such as cell culturing [146], biomedical research [149], organic synthesis [150].
Luminescent sensors are very much appropriate for microfluidic applications, real-time analytical data of
small molecules (ions, glucose, etc.) or process parameters (pH, oxygen, and temperature) due to their
high sensitivity, ease of miniaturization, the ability of contactless read-out, and their low cost [151][152].

Josef et al. presented a influential online microfluidic analysis setup for the detection of oxygen and pH
simultaneously according to figure 15 (i). The oxygen indicator platinum (II) meso-tetra (4-fluorophenyl)
tetrabenzoporphyrin (PtTPTBPF) was introduced into the polystyrene core (oxygen nanosensors) and a
pH-sensitive BF2-chelated tetraarylazadipyrromethene dye (aza-BODIPY) was entrapped into the
polyvinylpyrrolidone shell (pH nanosensors)[153]. There is a increasing importance to integrated sensors
to microfluidic bioreactors and organ-on-chip platforms. Sayed et al. developed a multi-analyte optical
sensing module for measurements of dissolved oxygen levels and pH level [154]. Sequence of device and
substrate used is shown in figure 15 (ii).

Figure 15- (i) Schematic of the nano-sensors measurement device[153] (ii) Fabricated devices Exploded
view of the sensing module for pH and oxygen detection[154]

Pfeiffer et al. developed a technique for determination of pH values and dissolved oxygen (DO) into
available all-glass microfluidic reactors (of very small sizes 43±3 μm for both DO and pH sensors) by
integration of luminescent sensors with a mask less photopolymerization[155].
Table 3 - Summary of some microfluidic device and detection scheme for contaminates available in
wastewater

Contaminants Mode of Substrate Fabrication Limit of Reference

detection method Detection s
2,4- Fluorescence Cellulose Wax printing 90 nM [156]
Dichlorophenox paper
yacetic acid
(2,4-D) pesticide
E. coli Polymerase PMMA Lithography 6 CFU [157]
chain reaction
E. coli Light scattering Chromatograp Photolithography 10 CFU/ml [158]
hy paper
Organophospha Acetylcholineste Whatman Wax printing 0.02 mg L-1 [159]
te and rase (AChE) paper
carbamate inhibition
pesticides
Organophospho Surface- Polymer Laser printing 10-12 M [160]
rus pesticides enhanced Raman
scattering
Carbofuran and Surface- Silicon wafer Photolithography 5 ppb [161]
Alachlor enhanced Raman
pesticide scattering
Nitrite, nitrate, Colorimetric Polycarbonate CNC milling 507 nm, [162]
ammonium, plate 507 nm,
orthophosphate 452 nm,
, and silicate 880 nm,
655 nm,
respectivel
y
Nitrate and Colorimetric PMMA Micro milling 0.025 µm, [163]
Nitrite 0.02 µm
respectivel
y
Nitrate Colorimetric Chromatograp Wax printing 0.53 ppm [164]
hy paper
Nitrate Electrochemical Graphene Liquid 0.01 mg L-1 [165]
foam photopolymerizatio
n
pH and dissolve Optical PMMA, PDMS Laser cutting - [154]
oxygen
Glucose and Electrochemical PDMS, Si Photolithography 50 μmol L−1 [166]
oxygen wafer
Dichlorvos Chemiluminesce Whatman Cutting 3.6 ng mL−1 [167]
nce chromatograp
hy paper
6. Conclusion and Future Perspective
Being one of the most problematic environmental pollutants, metallic ions including heavy metals and
other contaminants present in the water may cause severe health issues to human being and animals as
well. In this presented review we discussed about various types of microfluidic analytical device, their
capabilities and applicability. Herein we also discussed about different kind of fabrication techniques such
as; soft lithography, xurography, and µPADs in the development of microfluidic devices. Dozens of
detection scheme are available for contaminants detection in wastewater viz. electrochemical,
fluorescence, colorimetric, etc. It has been found that at present colorimetric is best detection scheme
for heavy metal ions and fluorescence is for biological contaminates. Detection of heavy metals and other
contaminants in terms of miniaturized devices development needs to be explored more. Also, cheap
fabrication method with high resolution and low limit of detection are still in transient period. In summary,
this review article will surely provide the researchers an insight to the microfluidics devices available for
ionic presence detection in the water sample.

Acknowledgements
Authors would like to acknowledge Start Research Grant provided by Science and Engineering Research
Board (SERB), DST, Government of India.

References
[1] Y. Lu et al., “Impacts of soil and water pollution on food safety and health risks in
China,” Environ. Int., vol. 77, pp. 5–15, Apr. 2015, doi: 10.1016/j.envint.2014.12.010.
[2] J. De Zuane, “Handbook of Drinking Water Quality,” Handb. Drink. Water Qual., 1996,
doi: 10.1002/9780470172971.
[3] K. Seraphin, “Inhibiting factors in the strategic financial management decision making
process: Evidence from South African SMMEs,” African J. Bus. Manag., vol. 9, no. 11,
pp. 490–500, Jun. 2015, doi: 10.5897/ajbm2014.7631.
[4] S. Ibrahim, M. Azab El-Liethy, A. L. K. Abia, M. Abdel-Gabbar, A. Mahmoud Al Zanaty,
and M. Mohamed Kamel, “Design of a bioaugmented multistage biofilter for accelerated
municipal wastewater treatment and deactivation of pathogenic microorganisms,” Sci.
Total Environ., vol. 703, Feb. 2020, doi: 10.1016/j.scitotenv.2019.134786.
[5] Q. Y. Chen, T. DesMarais, and M. Costa, “Metals and mechanisms of carcinogenesis,”
Annual Review of Pharmacology and Toxicology, vol. 59. Annual Reviews Inc., pp. 537–
554, 06-Jan-2019, doi: 10.1146/annurev-pharmtox-010818-021031.
[6] N. Sharma, A. Nigam, D. Lobanov, A. Gupta, A. Novikov, and M. Kumar, “Mercury (II)
Ion Detection using AgNWs-MoS2 Nanocomposite on GaN HEMT for IoT Enabled
Smart Water Quality Analysis,” IEEE Internet Things J., 2021, doi:
10.1109/JIOT.2021.3071382.
[7] S. Bhattacharya, A. B. Gupta, A. Gupta, and A. Pandey, Eds., Water Remediation.
Singapore: Springer Singapore, 2018.
[8] V. Mandal, “Status of Arsenic Toxicity in Ground Water in West Bengal, India: A
Review,” MOJ Toxicol., vol. 3, no. 5, Aug. 2017, doi: 10.15406/mojt.2017.03.00063.
[9] J. N. Edokpayi, J. O. Odiyo, and O. S. Durowoju, “Impact of Wastewater on Surface
 Water Quality in Developing Countries: A Case Study of South Africa,” in Water Quality,
InTech, 2017.
[10] V. A. Lemos and A. L. De Carvalho, “Determination of cadmium and lead in human
biological samples by spectrometric techniques: A review,” Environmental Monitoring
and Assessment, vol. 171, no. 1–4. Springer, pp. 255–265, 22-Dec-2010, doi:
10.1007/s10661-009-1276-z.
[11] D. J. Butcher, “Advances in inductively coupled plasma optical emission spectrometry for
environmental analysis,” Instrumentation Science and Technology, vol. 38, no. 6. Taylor
& Francis Group , pp. 458–469, Nov-2010, doi: 10.1080/10739149.2010.517884.
[12] J. Feldmann, P. Salaün, and E. Lombi, “Critical review perspective: elemental speciation
analysis methods in environmental chemistry - moving towards methodological
integration,” Environ. Chem., vol. 6, no. 4, p. 275, 2009, doi: 10.1071/EN09018.
[13] M. R. Sohrabi, Z. Matbouie, A. A. Asgharinezhad, and A. Dehghani, “Solid phase
extraction of Cd(II) and Pb(II) using a magnetic metal-organic framework, and their
determination by FAAS,” Microchim. Acta, vol. 180, no. 7–8, pp. 589–597, Jun. 2013,
doi: 10.1007/s00604-013-0952-4.
[14] B. K. Gale et al., “A review of current methods in microfluidic device fabrication and
future commercialization prospects,” Inventions, vol. 3, no. 3. MDPI Multidisciplinary
Digital Publishing Institute, 01-Sep-2018, doi: 10.3390/inventions3030060.
[15] H. S. Santana, J. L. Silva, B. Aghel, and J. Ortega-Casanova, “Review on microfluidic
device applications for fluids separation and water treatment processes,” SN Applied
Sciences, vol. 2, no. 3. Springer Nature, 01-Mar-2020, doi: 10.1007/s42452-020-2176-7.
[16] J. Gilmore, M. Islam, and R. Martinez-Duarte, “Challenges in the use of compact disc-
based centrifugal microfluidics for healthcare diagnostics at the extreme point of care,”
Micromachines, vol. 7, no. 4. MDPI AG, 2016, doi: 10.3390/mi7040052.
[17] M. Nayak et al., “Integrated sorting, concentration and real time PCR based detection
system for sensitive detection of microorganisms,” Sci. Rep., vol. 3, pp. 1–7, 2013, doi:
10.1038/srep03266.
[18] A. G. Niculescu, C. Chircov, A. C. Bîrcă, and A. M. Grumezescu, “Fabrication and
applications of microfluidic devices: A review,” International Journal of Molecular
Sciences, vol. 22, no. 4. MDPI AG, pp. 1–26, 02-Feb-2021, doi: 10.3390/ijms22042011.
[19] M. Islam, R. Natu, and R. Martinez-Duarte, “A study on the limits and advantages of
using a desktop cutter plotter to fabricate microfluidic networks,” Microfluid.
Nanofluidics, vol. 19, no. 4, pp. 973–985, Oct. 2015, doi: 10.1007/s10404-015-1626-9.
[20] T. Akyazi, L. Basabe-Desmonts, and F. Benito-Lopez, “Review on microfluidic paper-
based analytical devices towards commercialisation,” Analytica Chimica Acta, vol. 1001.
Elsevier B.V., pp. 1–17, 25-Feb-2018, doi: 10.1016/j.aca.2017.11.010.
[21] A. Atwe, A. Gupta, R. Kant, M. Das, I. Sharma, and S. Bhattacharya, “A novel
microfluidic switch for pH control using Chitosan based hydrogels,” Microsyst. Technol.,
vol. 20, no. 7, pp. 1373–1381, 2014, doi: 10.1007/s00542-014-2112-0.
[22] J. R. Mejía-Salazar, K. R. Cruz, E. M. M. Vásques, and O. N. de O. Jr., “Microfluidic
Point-of-Care Devices: New Trends and Future Prospects for eHealth Diagnostics,”
Sensors 2020, Vol. 20, Page 1951, vol. 20, no. 7, p. 1951, Mar. 2020, doi:
10.3390/S20071951.
[23] K. K. Borah, B. Bhuyan, and H. P. Sarma, “Lead, arsenic, fluoride, and iron
contamination of drinking water in the tea garden belt of Darrang district, Assam, India,”
 Environ. Monit. Assess. 2009 1691, vol. 169, no. 1, pp. 347–352, Oct. 2009, doi:
10.1007/S10661-009-1176-2.
[24] S. Bhattacharya, A. B. Gupta, A. Gupta, and A. Pandey, “Introduction to Water
Remediation: Importance and Methods,” 2018, pp. 3–8.
[25] A. K. Yetisen, M. S. Akram, and C. R. Lowe, “Paper-based microfluidic point-of-care
diagnostic devices,” Lab on a Chip, vol. 13, no. 12. Royal Society of Chemistry, pp.
2210–2251, 21-Jun-2013, doi: 10.1039/c3lc50169h.
[26] A. V. Gabrielyan, G. A. Shahnazaryan, and S. H. Minasyan, “Distribution and
Identification of Sources of Heavy Metals in the Voghji River Basin Impacted by Mining
Activities (Armenia),” J. Chem., vol. 2018, pp. 1–9, 2018, doi: 10.1155/2018/7172426.
[27] V. Masindi and K. L. Muedi, “Environmental Contamination by Heavy Metals,” in Heavy
Metals, InTech, 2018.
[28] B. Dai et al., “Schiff base-chitosan grafted multiwalled carbon nanotubes as a novel solid-
phase extraction adsorbent for determination of heavy metal by ICP-MS,” J. Hazard.
Mater., vol. 219–220, pp. 103–110, Jun. 2012, doi: 10.1016/j.jhazmat.2012.03.065.
[29] G. Matta and L. Gjyli, “Mercury, lead and arsenic: impact on environment and human
health,” Accessed: 26-Jul-2021. [Online]. Available: www.jchps.com.
[30] P. B. Tchounwou, C. G. Yedjou, A. K. Patlolla, and D. J. Sutton, “Heavy metal toxicity
and the environment,” EXS, vol. 101. NIH Public Access, pp. 133–164, 2012, doi:
10.1007/978-3-7643-8340-4_6.
[31] M. L. Riess and J. K. Halm, “Lead poisoning in an adult: Lead mobilization by
pregnancy?,” J. Gen. Intern. Med., vol. 22, no. 8, pp. 1212–1215, Aug. 2007, doi:
10.1007/s11606-007-0253-x.
[32] M. F. Wolfe, S. Schwarzbach, and R. A. Sulaiman, “Effects of mercury on wildlife: A
comprehensive review,” Environ. Toxicol. Chem., vol. 17, no. 2, pp. 146–160, Feb. 1998,
doi: 10.1002/ETC.5620170203.
[33] A. Stacchiotti et al., “Stress proteins and oxidative damage in a renal derived cell line
exposed to inorganic mercury and lead,” Toxicology, vol. 264, no. 3, pp. 215–224, Oct.
2009, doi: 10.1016/J.TOX.2009.08.014.
[34] “Basic Information about Lead in Drinking Water | US EPA.”
https://www.epa.gov/ground-water-and-drinking-water/basic-information-about-lead-
drinking-water (accessed Jul. 27, 2021).
[35] M. Jaishankar, T. Tseten, N. Anbalagan, B. B. Mathew, and K. N. Beeregowda, “Toxicity,
mechanism and health effects of some heavy metals,” Interdisciplinary Toxicology, vol. 7,
no. 2. Slovak Toxicology Society, pp. 60–72, 01-Jun-2014, doi: 10.2478/intox-2014-0009.
[36] M. Nishijo, H. Nakagawa, Y. Suwazono, K. Nogawa, and T. Kido, “Causes of death in
patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested
case–control analysis of a follow-up study in Japan,” BMJ Open, vol. 7, no. 7, p. e015694,
Jul. 2017, doi: 10.1136/BMJOPEN-2016-015694.
[37] P. B. Tchounwou, J. A. Centeno, and A. K. Patlolla, “Arsenic toxicity, mutagenesis, and
carcinogenesis - A health risk assessment and management approach,” Molecular and
Cellular Biochemistry, vol. 255, no. 1–2. Springer, pp. 47–55, Jan-2004, doi:
10.1023/B:MCBI.0000007260.32981.b9.
[38] M. F. Hughes, “Arsenic toxicity and potential mechanisms of action,” Toxicol. Lett., vol.
133, no. 1, pp. 1–16, Jul. 2002, doi: 10.1016/S0378-4274(02)00084-X.
[39] K. Phan et al., “Health risk assessment of inorganic arsenic intake of Cambodia residents
 through groundwater drinking pathway,” Water Res., vol. 44, no. 19, pp. 5777–5788, Nov.
2010, doi: 10.1016/j.watres.2010.06.021.
[40] N. X. Wang, Y. Y. Liu, Z. B. Wei, L. Y. Yang, and A. J. Miao, “Waterborne and
Dietborne Toxicity of Inorganic Arsenic to the Freshwater Zooplankton Daphnia magna,”
Environ. Sci. Technol., vol. 52, no. 15, pp. 8912–8919, Aug. 2018, doi:
10.1021/acs.est.8b02600.
[41] L. T. Budnik and L. Casteleyn, “Mercury pollution in modern times and its socio-medical
consequences,” Sci. Total Environ., vol. 654, pp. 720–734, Mar. 2019, doi:
10.1016/j.scitotenv.2018.10.408.
[42] M. Su, F. Barrueto, and R. S. Hoffman, “Childhood lead poisoning from paint chips: a
continuing problem,” J. Urban Heal. 2002 794, vol. 79, no. 4, pp. 491–501, Dec. 2002,
doi: 10.1093/JURBAN/79.4.491.
[43] M. C. Houston, “Role of Mercury Toxicity in Hypertension, Cardiovascular Disease, and
Stroke,” J. Clin. Hypertens., vol. 13, no. 8, pp. 621–627, Aug. 2011, doi: 10.1111/j.1751-
7176.2011.00489.x.
[44] A. L. Wani, A. Ara, and J. A. Usmani, “Lead toxicity: A review,” Interdisciplinary
Toxicology, vol. 8, no. 2. Slovak Toxicology Society, pp. 55–64, 01-Jun-2015, doi:
10.1515/intox-2015-0009.
[45] Y. Fan et al., “Modification of association between prior lung disease and lung cancer by
inhaled arsenic: A prospective occupational-based cohort study in Yunnan, China,” J.
Expo. Sci. Environ. Epidemiol., vol. 26, no. 5, pp. 464–470, Sep. 2016, doi:
10.1038/jes.2016.22.
[46] A. Rani, A. Kumar, A. Lal, and M. Pant, “Cellular mechanisms of cadmium-induced
toxicity: A review,” International Journal of Environmental Health Research, vol. 24, no.
4. Taylor and Francis Ltd., pp. 378–399, 04-Jul-2014, doi:
10.1080/09603123.2013.835032.
[47] J. M. Moulis and F. Thévenod, “New perspectives in cadmium toxicity: An introduction,”
BioMetals, vol. 23, no. 5. Kluwer Academic Publishers, pp. 763–768, 15-Jul-2010, doi:
10.1007/s10534-010-9365-6.
[48] A. Doltra et al., “Magnetic Resonance Imaging of Cardiovascular Fibrosis and
Inflammation: From Clinical Practice to Animal Studies and Back Cardiovascular MRI
View project Magnetic Resonance Imaging of Cardiovascular Fibrosis and Inflammation:
From Clinical Practice to Ani,” Biomed Res. Int., vol. 676489, no. 10, pp. 1–2, 2013, doi:
10.1155/2013.
[49] K. K. Das, S. N. Das, and S. A. Dhundasi, “Nickel, its adverse health effects & oxidative
stress,” Indian Journal of Medical Research, vol. 128, no. 4. pp. 412–425, 2008.
[50] M. Yeganeh et al., “Mapping of human health risks arising from soil nickel and mercury
contamination,” J. Hazard. Mater., vol. 244–245, pp. 225–239, Jan. 2013, doi:
10.1016/j.jhazmat.2012.11.040.
[51] M. L. Dotaniya, J. K. Thakur, V. D. Meena, D. K. Jajoria, and G. Rathor, “Chromium
pollution: A threat to environment-A review,” Agric. Rev., vol. 35, no. 2, p. 153, 2014,
doi: 10.5958/0976-0741.2014.00094.4.
[52] M. Mohanty and H. K. Patra, “Attenuation of chromium toxicity by bioremediation
technology,” Rev. Environ. Contam. Toxicol., vol. 210, pp. 1–34, 2011, doi: 10.1007/978-
1-4419-7615-4_1.
[53] S. Chowdhury, M. A. J. Mazumder, O. Al-Attas, and T. Husain, “Heavy metals in
 drinking water: Occurrences, implications, and future needs in developing countries,”
Science of the Total Environment, vol. 569–570. Elsevier B.V., pp. 476–488, 01-Nov-
2016, doi: 10.1016/j.scitotenv.2016.06.166.
[54] S. Selvaraj, S. Krishnaswamy, V. Devashya, S. Sethuraman, and U. M. Krishnan,
“Investigations on membrane perturbation by chrysin and its copper complex using self-
assembled lipid bilayers,” Langmuir, vol. 27, no. 21, pp. 13374–13382, Nov. 2011, doi:
10.1021/la2029356.
[55] “ATSDR - Public Health Statement: Copper.”
https://www.atsdr.cdc.gov/phs/phs.asp?id=204&tid=37 (accessed Aug. 06, 2020).
[56] B. A. Parmanand, L. Kellingray, G. Le Gall, A. W. Basit, S. Fairweather-Tait, and A.
Narbad, “A decrease in iron availability to human gut microbiome reduces the growth of
potentially pathogenic gut bacteria; an in vitro colonic fermentation study,” J. Nutr.
Biochem., vol. 67, pp. 20–27, May 2019, doi: 10.1016/j.jnutbio.2019.01.010.
[57] “Toxicity, mechanism and health effects of some heavy metals in: Interdisciplinary
Toxicology Volume 7 Issue 2 (2014).”
https://content.sciendo.com/view/journals/intox/7/2/article-p60.xml (accessed Apr. 07,
2020).
[58] A. H. Panhwar et al., “Correlation of cadmium and aluminum in blood samples of kidney
disorder patients with drinking water and tobacco smoking: related health risk,” Environ.
Geochem. Health, vol. 38, no. 1, pp. 265–274, Feb. 2016, doi: 10.1007/s10653-015-9715-
y.
[59] K. Klotz, W. Weistenhöfer, F. Neff, A. Hartwig, C. Van Thriel, and H. Drexler, “The
health effects of aluminum exposure,” Dtsch. Arztebl. Int., vol. 114, no. 39, pp. 653–659,
Sep. 2017, doi: 10.3238/arztebl.2017.0653.
[60] B. A. Kilfoy et al., “Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-
AARP Diet and Health Study,” Int. J. Cancer, vol. 129, no. 1, pp. 160–172, Jul. 2011, doi:
10.1002/ijc.25650.
[61] J. Chen, H. Wu, H. Qian, and Y. Gao, “Assessing Nitrate and Fluoride Contaminants in
Drinking Water and Their Health Risk of Rural Residents Living in a Semiarid Region of
Northwest China,” Expo. Heal., vol. 9, no. 3, pp. 183–195, Sep. 2017, doi:
10.1007/s12403-016-0231-9.
[62] H. Bagheri, A. Hajian, M. Rezaei, and A. Shirzadmehr, “Composite of Cu metal
nanoparticles-multiwall carbon nanotubes-reduced graphene oxide as a novel and high
performance platform of the electrochemical sensor for simultaneous determination of
nitrite and nitrate,” J. Hazard. Mater., vol. 324, pp. 762–772, Feb. 2017, doi:
10.1016/j.jhazmat.2016.11.055.
[63] K. Fajerwerg, V. Ynam, B. Chaudret, V. Garçon, D. Thouron, and M. Comtat, “An
original nitrate sensor based on silver nanoparticles electrodeposited on a gold electrode,”
Electrochem. commun., vol. 12, no. 10, pp. 1439–1441, Oct. 2010, doi:
10.1016/j.elecom.2010.08.003.
[64] A. Agrawal, R. S. Pandey, and B. Sharma, “Water Pollution with Special Reference to
Pesticide Contamination in India,” J. Water Resour. Prot., vol. 02, no. 05, pp. 432–448,
May 2010, doi: 10.4236/jwarp.2010.25050.
[65] J. A. Soller, T. Bartrand, N. J. Ashbolt, J. Ravenscroft, and T. J. Wade, “Estimating the
primary etiologic agents in recreational freshwaters impacted by human sources of faecal
contamination,” Water Res., vol. 44, no. 16, pp. 4736–4747, Sep. 2010, doi:
 10.1016/j.watres.2010.07.064.
[66] H. Behnam, S. Saeedfar, and F. Sabbagh, “Biological Contamination of the Water and Its
Effects Table1 : Microbial diseases originating in water,” no. 1999, 2013.
[67] G. Bhatt and S. Bhattacharya, “Novel Dipstick model for Portable Bio-sensing
Application Journal of Energy and Environmental Sustainability,” J. Energy Environ.
Sustain., vol. 7, pp. 32–35, 2019, [Online]. Available:
https://www.researchgate.net/publication/334762489.
[68] Q. Han, L. ping Qiu, R. zhen Cheng, and al -, “IOP Conference Series: Earth and
Environmental Science A Review on Advanced Treatment of Pharmaceutical Wastewater
Related content Study on Treatment of Secondary Tailwater of Wastewater Treatment
Plant by New Reinforced Flocculation Sedimentation Pengfei Yu and Yating He-Review
on Physicochemical, Chemical, and Biological Processes for Pharmaceutical Wastewater
Zhenchen Li and Ping Yang-Ceramic Membrane Coupling Process for Advanced
Treatment of Electroplating Wastewater Recent citations,” IOP Conf. Ser. Earth Environ.
Sci, vol. 63, p. 12025, doi: 10.1088/1755-1315/63/1/012025.
[69] P. M. Glibert, “Eutrophication, harmful algae and biodiversity — Challenging paradigms
in a world of complex nutrient changes,” Mar. Pollut. Bull., vol. 124, no. 2, pp. 591–606,
Nov. 2017, doi: 10.1016/j.marpolbul.2017.04.027.
[70] F. Nouban and M. Abazid, “Plastic degrading fungi Trichoderma viride and Aspergillus
nomius isolated fromNouban, F. and Abazid, M. (2017) ‘Plastic degrading fungi
Trichoderma viride and Aspergillus nomius isolated from local landfill soil in Medan’,
Iopscience.Iop.Org, 8(February ,” Iopscience.Iop.Org, vol. 8, no. February 2018, pp. 68–
74, Aug. 2017, doi: 10.1088/1755-1315.
[71] L. Knobeloch, B. Salna, A. Hogan, J. Postle, and H. Anderson, “Blue babies and nitrate-
contaminated well water,” Environ. Health Perspect., vol. 108, no. 7, pp. 675–678, 2000,
doi: 10.1289/ehp.00108675.
[72] J. Kudr, O. Zitka, M. Klimanek, R. Vrba, and V. Adam, “Microfluidic electrochemical
devices for pollution analysis–A review,” Sensors Actuators B Chem., vol. 246, pp. 578–
590, Jul. 2017, doi: 10.1016/J.SNB.2017.02.052.
[73] J. Kudr, O. Zitka, M. Klimanek, R. Vrba, and V. Adam, “Microfluidic electrochemical
devices for pollution analysis–A review,” Sensors and Actuators, B: Chemical, vol. 246.
Elsevier B.V., pp. 578–590, 01-Jan-2017, doi: 10.1016/j.snb.2017.02.052.
[74] A. Amine and H. Mohammadi, “Amperometry,” Encycl. Anal. Sci., pp. 85–98, Jan. 2019,
doi: 10.1016/B978-0-12-409547-2.14204-0.
[75] P. Kubáň and P. C. Hauser, “Contactless conductivity detection for analytical techniques-
Developments from 2012 to 2014,” Electrophoresis, vol. 36, no. 1. Wiley-VCH Verlag,
pp. 195–211, 01-Jan-2015, doi: 10.1002/elps.201400336.
[76] G. Aragay and A. Merkoçi, “Nanomaterials application in electrochemical detection of
heavy metals,” Electrochim. Acta, vol. 84, no. 84, pp. 49–61, Dec. 2012, doi:
10.1016/j.electacta.2012.04.044.
[77] S. Cinti, D. Moscone, and F. Arduini, “Preparation of paper-based devices for reagentless
electrochemical (bio)sensor strips,” Nat. Protoc., vol. 14, no. 8, pp. 2437–2451, 2019, doi:
10.1038/s41596-019-0186-y.
[78] J. Shu and D. Tang, “Current Advances in Quantum-Dots-Based Photoelectrochemical
Immunoassays,” Chemistry - An Asian Journal, vol. 12, no. 21. John Wiley and Sons Ltd,
pp. 2780–2789, 02-Nov-2017, doi: 10.1002/asia.201701229.
[79] W. W. Zhao, J. J. Xu, and H. Y. Chen, “Photoelectrochemical bioanalysis: The state of the
art,” Chemical Society Reviews, vol. 44, no. 3. Royal Society of Chemistry, pp. 729–741,
07-Feb-2015, doi: 10.1039/c4cs00228h.
[80] L. M. Fu and Y. N. Wang, “Detection methods and applications of microfluidic paper-
based analytical devices,” TrAC Trends Anal. Chem., vol. 107, pp. 196–211, Oct. 2018,
doi: 10.1016/J.TRAC.2018.08.018.
[81] R. Szczypiński et al., “Fluorescence detection in microfluidics systems.”
[82] G. Morbioli, T. Mazzu-Nascimento, … A. S.-A. chimica, and undefined 2017, “Technical
aspects and challenges of colorimetric detection with microfluidic paper-based analytical
devices (μPADs)-A review,” Elsevier, Accessed: 31-Jul-2021. [Online]. Available:
https://www.sciencedirect.com/science/article/pii/S0003267017303483.
[83] X. Jiang and Z. H. Fan, “Fabrication and Operation of Paper-Based Analytical Devices,”
Annu. Rev. Anal. Chem., vol. 9, no. 1, pp. 203–222, Jun. 2016, doi: 10.1146/annurev-
anchem-071015-041714.
[84] J. Moral-Vico et al., “Dual chronoamperometric detection of enzymatic biomarkers using
magnetic beads and a low-cost flow cell,” Biosens. Bioelectron., vol. 69, pp. 328–336, Jul.
2015, doi: 10.1016/j.bios.2015.02.042.
[85] F. Gaitan, N. Apazidis, and V. Eliasson, “To cite this article: Scott Brittain et al,” Phys.
World, vol. 11, no. 5, p. 31, 1998.
[86] R. K. Singh, R. Kant, S. Singh, E. Suresh, A. Gupta, and S. Bhattacharya, “A novel helical
micro-valve for embedded micro-fluidic applications,” Microfluid. Nanofluidics, vol. 19,
no. 1, pp. 19–29, 2015, doi: 10.1007/s10404-015-1543-y.
[87] R. K. Singh, A. Kumar, R. Kant, A. Gupta, E. Suresh, and S. Bhattacharya, “Design and
fabrication of 3-dimensional helical structures in polydimethylsiloxane for flow control
applications,” Microsyst. Technol., vol. 20, no. 1, pp. 101–111, 2014, doi:
10.1007/s00542-013-1738-7.
[88] A. Kumar et al., “Optimization of laser machining process for the preparation of
photomasks, and its application to microsystems fabrication,” J. Micro/Nanolithography,
MEMS, MOEMS, vol. 12, no. 4, p. 041203, 2013, doi: 10.1117/1.jmm.12.4.041203.
[89] Y. Zhang, J. Liu, H. Wang, and Y. Fan, “Laser-induced selective wax reflow for paper-
based microfluidics,” RSC Adv., vol. 9, no. 20, pp. 11460–11464, Apr. 2019, doi:
10.1039/C9RA00610A.
[90] X. Li, J. Tian, G. Garnier, and W. Shen, “Fabrication of paper-based microfluidic sensors
by printing,” Colloids Surfaces B Biointerfaces, vol. 76, no. 2, pp. 564–570, Apr. 2010,
doi: 10.1016/j.colsurfb.2009.12.023.
[91] A. Teichler, J. Perelaer, and U. S. Schubert, “Inkjet printing of organic electronics-
comparison of deposition techniques and state-of-the-art developments,” J. Mater. Chem.
C, vol. 1, no. 10, pp. 1910–1925, Mar. 2013, doi: 10.1039/c2tc00255h.
[92] T. Okamoto, T. Suzuki, and N. Yamamoto, “Microarray fabrication with covalent
attachment of DNA using Bubble Jet technology,” Nat. Biotechnol., vol. 18, no. 4, pp.
438–441, 2000, doi: 10.1038/74507.
[93] K. Yamada, T. G. Henares, K. Suzuki, and D. Citterio, “Paper-based inkjet-printed
microfluidic analytical devices,” Angew. Chemie - Int. Ed., vol. 54, no. 18, pp. 5294–
5310, 2015, doi: 10.1002/anie.201411508.
[94] C. L. Sones et al., “Laser-induced photo-polymerisation for creation of paper-based
fluidic devices,” Lab Chip, vol. 14, no. 23, pp. 4567–4574, Dec. 2014, doi:
 10.1039/c4lc00850b.
[95] P. J. W. He, I. N. Katis, R. W. Eason, and C. L. Sones, “Laser-based patterning for fluidic
devices in nitrocellulose,” Biomicrofluidics, vol. 9, no. 2, p. 026503, Apr. 2015, doi:
10.1063/1.4919629.
[96] S. Paul, R. Singh, and W. Yan, “Lasers Based Manufacturing,” no. June 2016, 2015, doi:
10.1007/978-81-322-2352-8.
[97] S. Paul, R. Singh, and W. Yan, Lasers Based Manufacturing, no. June 2016. 2015.
[98] Y. Sameenoi, P. Na Nongkai, S. Nouanthavong, C. S. Henry, and D. Nacaprich, “One-step
polymer screen-printing for microfluidic paper-based analytical device (¼PAD)
fabrication,” Analyst, vol. 139, no. 24, pp. 6580–6588, Nov. 2014, doi:
10.1039/c4an01624f.
[99] A. Z. Qamar and M. H. Shamsi, “Desktop fabrication of lab-on-chip devices on flexible
substrates: A brief review,” Micromachines, vol. 11, no. 2, 2020, doi:
10.3390/mi11020126.
[100] J. Kim and R. Surapaneni, “Rapid prototyping of microfluidic systems using a
PDMS/polymer tape composite Sperm separation from mTESE sample View project
Implantable bioreactor for treatment of segmental bone defects View project,”
pubs.rsc.org, 2009, doi: 10.1039/b818389a.
[101] D. A. Bartholomeusz, R. W. Boutté, and J. D. Andrade, “Xurography: Rapid prototyping
of microstructures using a cutting plotter,” J. Microelectromechanical Syst., vol. 14, no. 6,
pp. 1364–1374, Dec. 2005, doi: 10.1109/JMEMS.2005.859087.
[102] M. Islam, R. Natu, and R. Martinez-Duarte, “A study on the limits and advantages of
using a desktop cutter plotter to fabricate microfluidic networks,” Microfluid.
Nanofluidics, vol. 19, no. 4, pp. 973–985, Oct. 2015, doi: 10.1007/s10404-015-1626-9.
[103] R. Burger and J. Ducrée, “Handling and analysis of cells and bioparticles on centrifugal
microfluidic platforms,” Expert Review of Molecular Diagnostics, vol. 12, no. 4. pp. 407–
421, May-2012, doi: 10.1586/erm.12.28.
[104] I. Maguire, R. O’Kennedy, J. Ducrée, and F. Regan, “A review of centrifugal
microfluidics in environmental monitoring,” Analytical Methods, vol. 10, no. 13. Royal
Society of Chemistry, pp. 1497–1515, 07-Apr-2018, doi: 10.1039/c8ay00361k.
[105] R. Gorkin et al., “Centrifugal microfluidics for biomedical applications,” Lab on a Chip,
vol. 10, no. 14. Royal Society of Chemistry, pp. 1758–1773, 2010, doi:
10.1039/b924109d.
[106] A. Lace and J. Cleary, “A Review of Microfluidic Detection Strategies for Heavy Metals
in Water,” Chemosens. 2021, Vol. 9, Page 60, vol. 9, no. 4, p. 60, Mar. 2021, doi:
10.3390/CHEMOSENSORS9040060.
[107] N. Pourreza, H. Golmohammadi, and S. Rastegarzadeh, “Highly selective and portable
chemosensor for mercury determination in water samples using curcumin nanoparticles in
a paper based analytical device,” RSC Adv., vol. 6, no. 73, pp. 69060–69066, Jul. 2016,
doi: 10.1039/c6ra08879a.
[108] R. Meelapsom, P. Jarujamrus, M. Amatatongchai, S. Chairam, C. Kulsing, and W. Shen,
“Chromatic analysis by monitoring unmodified silver nanoparticles reduction on double
layer microfluidic paper-based analytical devices for selective and sensitive determination
of mercury(II),” Talanta, vol. 155, pp. 193–201, Aug. 2016, doi:
10.1016/j.talanta.2016.04.037.
[109] Q. Wu et al., “A paper-based microfluidic analytical device combined with home-made
 SPE column for the colorimetric determination of copper(II) ion,” Talanta, vol. 204, pp.
518–524, Nov. 2019, doi: 10.1016/j.talanta.2019.06.006.
[110] F. Li, Y. Hu, Z. Li, J. Liu, L. Guo, and J. He, “Three-dimensional microfluidic paper-
based device for multiplexed colorimetric detection of six metal ions combined with use
of a smartphone,” Anal. Bioanal. Chem., vol. 411, no. 24, pp. 6497–6508, Sep. 2019, doi:
10.1007/s00216-019-02032-5.
[111] Y. Guan and B. Sun, “Detection and extraction of heavy metal ions using paper-based
analytical devices fabricated via atom stamp printing,” Microsystems Nanoeng., vol. 6, no.
1, 2020, doi: 10.1038/s41378-019-0123-9.
[112] S. Yan et al., “Rapid, one-step preparation of SERS substrate in microfluidic channel for
detection of molecules and heavy metal ions,” Spectrochim. Acta - Part A Mol. Biomol.
Spectrosc., vol. 220, p. 117113, 2019, doi: 10.1016/j.saa.2019.05.018.
[113] L. L. Shen, G. R. Zhang, W. Li, M. Biesalski, and B. J. M. Etzold, “Modifier-Free
Microfluidic Electrochemical Sensor for Heavy-Metal Detection,” ACS Omega, vol. 2, no.
8, pp. 4593–4603, Aug. 2017, doi: 10.1021/acsomega.7b00611.
[114] Y. Hong et al., “3D Printed Microfluidic Device with Microporous Mn2O3-Modified
Screen Printed Electrode for Real-Time Determination of Heavy Metal Ions,” ACS Appl.
Mater. Interfaces, vol. 8, no. 48, pp. 32940–32947, Dec. 2016, doi:
10.1021/acsami.6b10464.
[115] F. Cortés-Salazar, S. Beggah, J. R. van der Meer, and H. H. Girault, “Electrochemical
As(III) whole-cell based biochip sensor,” Biosens. Bioelectron., vol. 47, pp. 237–242, Sep.
2013, doi: 10.1016/j.bios.2013.03.011.
[116] L. Wang et al., “Enhanced sensitivity and stability of room-temperature NH3 sensors
using core-shell CeO2 nanoparticles@cross-linked PANI with p-n heterojunctions,” ACS
Appl. Mater. Interfaces, vol. 6, no. 16, pp. 14131–14140, 2014, doi: 10.1021/am503286h.
[117] Y. Zhang, P. Zuo, and B. C. Ye, “A low-cost and simple paper-based microfluidic device
for simultaneous multiplex determination of different types of chemical contaminants in
food,” Biosens. Bioelectron., vol. 68, pp. 14–19, Jun. 2015, doi:
10.1016/j.bios.2014.12.042.
[118] G. Peng et al., “Highly sensitive and selective determination of Hg(II) based on
microfluidic chip with on-line fluorescent derivatization,” Spectrochim. Acta - Part A Mol.
Biomol. Spectrosc., vol. 204, pp. 1–6, Nov. 2018, doi: 10.1016/j.saa.2018.06.006.
[119] J. Qi et al., “Three-dimensional paper-based microfluidic chip device for multiplexed
fluorescence detection of Cu2+ and Hg2+ ions based on ion imprinting technology,”
Sensors Actuators, B Chem., vol. 251, pp. 224–233, Nov. 2017, doi:
10.1016/j.snb.2017.05.052.
[120] X. R. Wang, B. W. Li, H. Y. You, and L. X. Chen, “An ion imprinted polymers grafted
paper-based fluorescent sensor based on quantum dots for detection of Cu2+ ions,”
Chinese J. Anal. Chem., vol. 43, no. 10, pp. 1499–1504, Oct. 2015, doi: 10.1016/S1872-
2040(15)60867-2.
[121] H. Wang, Y. J. Li, J. F. Wei, J. R. Xu, Y. H. Wang, and G. X. Zheng, “Paper-based three-
dimensional microfluidic device for monitoring of heavy metals with a camera cell
phone,” Anal. Bioanal. Chem., vol. 406, no. 12, pp. 2799–2807, Mar. 2014, doi:
10.1007/s00216-014-7715-x.
[122] P. Nath, R. K. Arun, and N. Chanda, “A paper based microfluidic device for the detection
of arsenic using a gold nanosensor,” RSC Adv., vol. 4, no. 103, pp. 59558–59561, Nov.
 2014, doi: 10.1039/c4ra12946f.
[123] J. P. Devadhasan and J. Kim, “A chemically functionalized paper-based microfluidic
platform for multiplex heavy metal detection,” Sensors Actuators, B Chem., vol. 273, pp.
18–24, Nov. 2018, doi: 10.1016/j.snb.2018.06.005.
[124] H. Sharifi, J. Tashkhourian, and B. Hemmateenejad, “A 3D origami paper-based
analytical device combined with PVC membrane for colorimetric assay of heavy metal
ions: Application to determination of Cu(II) in water samples,” Anal. Chim. Acta, vol.
1126, pp. 114–123, Aug. 2020, doi: 10.1016/j.aca.2020.06.006.
[125] A. Bonyár et al., “A colorimetry based, semi-automated portable sensor device for the
detection of arsenic in drinking water,” Sensors Actuators, B Chem., vol. 251, pp. 1042–
1049, Nov. 2017, doi: 10.1016/j.snb.2017.06.119.
[126] Y. Guan and B. Sun, “Detection and extraction of heavy metal ions using paper-based
analytical devices fabricated via atom stamp printing,” Microsystems Nanoeng., vol. 6, no.
1, pp. 1–12, Dec. 2020, doi: 10.1038/s41378-019-0123-9.
[127] P. Kamnoet, W. Aeungmaitrepirom, R. F. Menger, and C. S. Henry, “Highly selective
simultaneous determination of Cu(ii), Co(ii), Ni(ii), Hg(ii), and Mn(ii) in water samples
using microfluidic paper-based analytical devices,” Analyst, vol. 146, no. 7, pp. 2229–
2239, Apr. 2021, doi: 10.1039/d0an02200d.
[128] X. Sun et al., “Improved assessment of accuracy and performance using a rotational
paper-based device for multiplexed detection of heavy metals,” Talanta, vol. 178, pp.
426–431, Feb. 2018, doi: 10.1016/j.talanta.2017.09.059.
[129] C. Fan, S. He, G. Liu, L. Wang, and S. Song, “A Portable and Power-Free Microfluidic
Device for Rapid and Sensitive Lead (Pb2+) Detection,” Sensors, vol. 12, no. 7, pp. 9467–
9475, Jul. 2012, doi: 10.3390/s120709467.
[130] M. A. Chowdury, N. Walji, M. A. Mahmud, and B. D. MacDonald, “Paper-based
microfluidic device with a gold nanosensor to detect arsenic contamination of
groundwater in Bangladesh,” Micromachines, vol. 8, no. 3, p. 71, Mar. 2017, doi:
10.3390/mi8030071.
[131] G. Wang, L. T. Chu, H. Hartanto, W. B. Utomo, R. A. Pravasta, and T. H. Chen,
“Microfluidic Particle Dam for Visual and Quantitative Detection of Lead Ions,” ACS
Sensors, vol. 5, no. 1, pp. 19–23, Jan. 2020, doi: 10.1021/acssensors.9b01945.
[132] A. Z, A. M, K. G, and U. Y, “A fully automated microfluidic-based electrochemical
sensor for real-time bacteria detection,” Biosens. Bioelectron., vol. 100, pp. 541–548, Feb.
2018, doi: 10.1016/J.BIOS.2017.09.046.
[133] E. Costa-Rama, H. P. A. Nouws, C. Delerue-Matos, M. C. Blanco-López, and M. T.
Fernández-Abedul, “Preconcentration and sensitive determination of the anti-
inflammatory drug diclofenac on a paper-based electroanalytical platform,” Anal. Chim.
Acta, vol. 1074, pp. 89–97, Oct. 2019, doi: 10.1016/J.ACA.2019.05.016.
[134] E. W. K. Young and D. J. Beebe, “Fundamentals of microfluidic cell culture in controlled
microenvironments,” Chemical Society Reviews, vol. 39, no. 3. The Royal Society of
Chemistry, pp. 1036–1048, 24-Mar-2010, doi: 10.1039/b909900j.
[135] Y. Sun, T. A. Haglund, A. J. Rogers, A. F. Ghanim, and P. Sethu, “Review: Microfluidics
technologies for blood-based cancer liquid biopsies,” Analytica Chimica Acta, vol. 1012.
Elsevier B.V., pp. 10–29, 05-Jul-2018, doi: 10.1016/j.aca.2017.12.050.
[136] F. Inci, Y. Saylan, A. M. Kojouri, M. G. Ogut, A. Denizli, and U. Demirci, “A disposable
microfluidic-integrated hand-held plasmonic platform for protein detection,” Appl. Mater.
 Today, vol. 18, p. 100478, Mar. 2020, doi: 10.1016/j.apmt.2019.100478.
[137] B. M. Jayawardane, S. Wei, I. D. McKelvie, and S. D. Kolev, “Microfluidic paper-based
analytical device for the determination of nitrite and nitrate,” Anal. Chem., vol. 86, no. 15,
pp. 7274–7279, Aug. 2014, doi: 10.1021/ac5013249.
[138] T. M. G. Cardoso, P. T. Garcia, and W. K. T. Coltro, “Colorimetric determination of
nitrite in clinical, food and environmental samples using microfluidic devices stamped in
paper platforms,” Anal. Methods, vol. 7, no. 17, pp. 7311–7317, 2015, doi:
10.1039/C5AY00466G.
[139] M. I. G. S. Almeida, B. M. Jayawardane, S. D. Kolev, and I. D. McKelvie,
“Developments of microfluidic paper-based analytical devices (μPADs) for water
analysis: A review,” Talanta, vol. 177, no. July 2017, pp. 176–190, 2018, doi:
10.1016/j.talanta.2017.08.072.
[140] P. Phansi et al., “Membraneless Gas-Separation Microfluidic Paper-Based Analytical
Devices for Direct Quantitation of Volatile and Nonvolatile Compounds,” Anal. Chem.,
vol. 88, no. 17, pp. 8749–8756, 2016, doi: 10.1021/acs.analchem.6b02103.
[141] P. S. Chauhan, A. Rai, A. Gupta, and S. Bhattacharya, “Enhanced photocatalytic
performance of vertically grown ZnO nanorods decorated with metals (Al, Ag, Au, and
Au-Pd) for degradation of industrial dye,” Mater. Res. Express, vol. 4, no. 5, May 2017,
doi: 10.1088/2053-1591/aa6d31.
[142] P. S. Chauhan, R. Kant, A. Rai, A. Gupta, and S. Bhattacharya, “Facile synthesis of
ZnO/GO nanoflowers over Si substrate for improved photocatalytic decolorization of MB
dye and industrial wastewater under solar irradiation,” Mater. Sci. Semicond. Process.,
vol. 89, no. August 2018, pp. 6–17, 2019, doi: 10.1016/j.mssp.2018.08.022.
[143] A. Gupta, J. R. Saurav, and S. Bhattacharya, “Solar light based degradation of organic
pollutants using ZnO nanobrushes for water filtration,” RSC Adv., vol. 5, no. 87, pp.
71472–71481, Aug. 2015, doi: 10.1039/c5ra10456d.
[144] A. Gupta, K. Mondal, A. Sharma, and S. Bhattacharya, “Superhydrophobic
polymethylsilsesquioxane pinned one dimensional ZnO nanostructures for water
remediation through photo-catalysis,” RSC Adv., vol. 5, no. 57, pp. 45897–45907, 2015,
doi: 10.1039/c5ra02938d.
[145] C. Sicard et al., “Tools for water quality monitoring and mapping using paper-based
sensors and cell phones,” Water Res., vol. 70, pp. 360–369, Mar. 2015, doi:
10.1016/j.watres.2014.12.005.
[146] C. D. Chin, V. Linder, and S. K. Sia, “Lab-on-a-chip devices for global health: Past
studies and future opportunities,” Lab on a Chip, vol. 7, no. 1. Royal Society of
Chemistry, pp. 41–57, 19-Dec-2007, doi: 10.1039/b611455e.
[147] J. El-Ali, P. K. Sorger, and K. F. Jensen, “Cells on chips,” Nature, vol. 442, no. 7101.
Nature Publishing Group, pp. 403–411, 27-Jul-2006, doi: 10.1038/nature05063.
[148] S. N. Bhatia and D. E. Ingber, “Microfluidic organs-on-chips,” Nature Biotechnology, vol.
32, no. 8. Nature Publishing Group, pp. 760–772, 05-Aug-2014, doi: 10.1038/nbt.2989.
[149] E. K. Sackmann, A. L. Fulton, and D. J. Beebe, “The present and future role of
microfluidics in biomedical research,” Nature, vol. 507, no. 7491. Nature Publishing
Group, pp. 181–189, 12-Mar-2014, doi: 10.1038/nature13118.
[150] B. Gutmann, D. Cantillo, and C. O. Kappe, “Continuous-flow technology - A tool for the
safe manufacturing of active pharmaceutical ingredients,” Angewandte Chemie -
International Edition, vol. 54, no. 23. Wiley-VCH Verlag, pp. 6688–6728, 01-Jun-2015,
 doi: 10.1002/anie.201409318.
[151] S. A. Pfeiffer and S. Nagl, “Microfluidic platforms employing integrated fluorescent or
luminescent chemical sensors: a review of methods, scope and applications,” Methods
Appl. Fluoresc., vol. 3, no. 3, p. 034003, Apr. 2015, doi: 10.1088/2050-6120/3/3/034003.
[152] S. Sun, B. Ungerböck, and T. Mayr, “Imaging of oxygen in microreactors and
microfluidic systems,” Methods Appl. Fluoresc., vol. 3, no. 3, p. 034002, Apr. 2015, doi:
10.1088/2050-6120/3/3/034002.
[153] J. Ehgartner et al., “Simultaneous Determination of Oxygen and pH Inside Microfluidic
Devices Using Core-Shell Nanosensors,” Anal. Chem., vol. 88, no. 19, pp. 9796–9804,
Oct. 2016, doi: 10.1021/acs.analchem.6b02849.
[154] S. A. M. Shaegh et al., “A microfluidic optical platform for real-time monitoring of pH
and oxygen in microfluidic bioreactors and organ-on-chip devices,” Biomicrofluidics, vol.
10, no. 4, Jul. 2016, doi: 10.1063/1.4955155.
[155] S. A. Pfeiffer, S. M. Borisov, and S. Nagl, “In-line monitoring of pH and oxygen during
enzymatic reactions in off-the-shelf all-glass microreactors using integrated luminescent
microsensors,” Microchim. Acta, vol. 184, no. 2, pp. 621–626, Feb. 2017, doi:
10.1007/s00604-016-2021-2.
[156] Z. Zhang, X. Ma, M. Jia, B. Li, J. Rong, and X. Yang, “Deposition of CdTe quantum dots
on microfluidic paper chips for rapid fluorescence detection of pesticide 2,4-D,” Analyst,
vol. 144, no. 4. Royal Society of Chemistry, pp. 1282–1291, 21-Feb-2019, doi:
10.1039/c8an02051e.
[157] U. Dharmasiri et al., “Enrichment and detection of escherichia coli O157:H7 from water
samples using an antibody modified microfluidic chip,” Anal. Chem., vol. 82, no. 7, pp.
2844–2849, Apr. 2010, doi: 10.1021/ac100323k.
[158] T. S. Park and J. Y. Yoon, “Smartphone detection of Escherichia coli from field water
samples on paper microfluidics,” IEEE Sens. J., vol. 15, no. 3, pp. 1902–1907, Mar. 2015,
doi: 10.1109/JSEN.2014.2367039.
[159] L. Jin et al., “A facile microfluidic paper-based analytical device for acetylcholinesterase
inhibition assay utilizing organic solvent extraction in rapid detection of pesticide residues
in food,” Anal. Chim. Acta, vol. 1100, pp. 215–224, Mar. 2020, doi:
10.1016/j.aca.2019.11.067.
[160] O. Guselnikova, P. Postnikov, R. Elashnikov, E. Miliutina, V. Svorcik, and O. Lyutakov,
“Metal-organic framework (MOF-5) coated SERS active gold gratings: A platform for the
selective detection of organic contaminants in soil,” Anal. Chim. Acta, vol. 1068, pp. 70–
79, Aug. 2019, doi: 10.1016/j.aca.2019.03.058.
[161] J. Parisi, Q. Dong, and Y. Lei, “In situ microfluidic fabrication of SERS nanostructures for
highly sensitive fingerprint microfluidic-SERS sensing,” RSC Adv., vol. 5, no. 19, pp.
14081–14089, 2015, doi: 10.1039/c4ra15174g.
[162] H. Hwang, Y. Kim, J. Cho, J. Y. Lee, M. S. Choi, and Y. K. Cho, “Lab-on-a-disc for
simultaneous determination of nutrients in water,” Anal. Chem., vol. 85, no. 5, pp. 2954–
2960, Mar. 2013, doi: 10.1021/ac3036734.
[163] A. D. Beaton et al., “Lab-on-chip measurement of nitrate and nitrite for in situ analysis of
natural waters,” Environ. Sci. Technol., vol. 46, no. 17, pp. 9548–9556, Sep. 2012, doi:
10.1021/es300419u.
[164] A. Charbaji, H. Heidari-Bafroui, C. Anagnostopoulos, and M. Faghri, “A new paper-based
microfluidic device for improved detection of nitrate in water,” Sensors (Switzerland), vol.
 21, no. 1, pp. 1–15, Jan. 2021, doi: 10.3390/s21010102.
[165] M. A. Ali et al., “In situ integration of graphene foam-titanium nitride based bio-scaffolds
and microfluidic structures for soil nutrient sensors,” Lab Chip, vol. 17, no. 2, pp. 274–
285, Jan. 2017, doi: 10.1039/C6LC01266C.
[166] N. Pereira Rodrigues, Y. Sakai, and T. Fujii, “Cell-based microfluidic biochip for the
electrochemical real-time monitoring of glucose and oxygen,” Sensors Actuators, B
Chem., vol. 132, no. 2, pp. 608–613, Jun. 2008, doi: 10.1016/j.snb.2007.12.025.
[167] W. Liu, J. Kou, H. Xing, and B. Li, “Paper-based chromatographic chemiluminescence
chip for the detection of dichlorvos in vegetables,” Biosens. Bioelectron., vol. 52, pp. 76–
81, Feb. 2014, doi: 10.1016/j.bios.2013.08.024.