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Abstract

An overview of the recent research works and trends in the design and fabrication of microfluidic devices and microfluidics-integrated biosensors for pollution analysis and monitoring of environmental contaminants is presented in this paper. In alignment with the tendency in miniaturization and integration into “lab on a chip” devices to reduce the use of reagents, energy, and implicit processing costs, the most common and newest materials used in the fabrication of microfluidic devices and microfluidics-integrated sensors and biosensors, the advantages and disadvantages of materials, fabrication methods, and the detection methods used for microfluidic environmental analysis are synthesized and evaluated.
Sustainability 2022, 14, 12844. https://doi.org/10.3390/su141912844 www.mdpi.com/journal/sustainability
Review
Microfluidic Devices and Microfluidics-Integrated
Electrochemical and Optical (Bio)Sensors for Pollution
Analysis: A Review
Badriyah Alhalaili 1, Ileana Nicoleta Popescu 2,*, Carmen Otilia Rusanescu 3 and Ruxandra Vidu ,4,5,*
1 Nanotechnology and Advanced Materials Program, Kuwait Institute for Scientific Research, P.O. Box 24885,
Safat 13109, Kuwait
2 Faculty of Materials Engineering and Mechanics, Valahia University of Targoviste, 13 Aleea Sinaia Street,
130004 Targoviste, Romania
3 Faculty of Biotechnical Systems Engineering, University POLITEHNICA of Bucharest,
060042 Bucharest, Romania
4 Faculty of Materials Science and Engineering, University POLITEHNICA of Bucharest,
060042 Bucharest, Romania
5 Department of Electrical and Computer Engineering, University of California Davis, Davis, CA 95616, USA
* Correspondence: ileana.nicoleta.popescu@valahia.ro (I.N.P.);
rvidu@ucdavis.edu (R.V.)
Abstract: An overview of the recent research works and trends in the design and fabrication of
microfluidic devices and microfluidics-integrated biosensors for pollution analysis and monitor-
ing of environmental contaminants is presented in this paper. In alignment with the tendency in
miniaturization and integration into “lab on a chip” devices to reduce the use of reagents, energy,
and implicit processing costs, the most common and newest materials used in the fabrication of
microfluidic devices and microfluidics-integrated sensors and biosensors, the advantages and
disadvantages of materials, fabrication methods, and the detection methods used for microfluidic
environmental analysis are synthesized and evaluated.
Keywords: microfluidic devices; optical/electrochemical sensors; (nano)biosensors; pollution
analysis; environmental contaminants monitoring
1. Introduction
Today, human society is facing significant pollution of the environment [15] and a
massive decrease in natural resources [69], leading implicitly to a decrease in the
quality of life. The sources of environmental pollution are the result either of natural
causes or human activities, such as continuous urbanization and industrialization,
excessive exploitation of natural resources, burning of fossil fuels, etc., which affect
human health and destroy the balance of the ecosystem. As a result, scientists have been
working together to find effective solutions for monitoring and reducing pollution
sources by developing advanced materials or exploiting micro/nanodevice fabrication
and integration of various processes in clean technologies for environmental
sustainability [1014].
One of these solutions is the use of microfluidic devices and microfluidics-
integrated (electrochemical/optical) biosensors for pollution analysis to obtain a quick,
accurate, reliable response and rapid diagnosis [9,1517]. The microfluidic devices allow
the integration and miniaturization of an entire laboratory on a very small scale,
allowing their integration in a simple and portable system [16], with the advantage of
significantly reducing the consumption of reagents, energy, time, and money [15].
Citation: Alhalaili, B.; Popescu, I.N.;
Rusanescu, C.O.; Vidu, R.
Microfluidic Devices and
Microfluidics-Integrated
Electrochemical and Optical
(Bio)Sensors for Pollution Analysis:
A review . Sustainability 2022, 14,
12844. https://doi.org/10.3390/
su141912844
Academic Editor: Marc A. Rosen
Received: 2 August 2022
Accepted: 25 September 2022
Published: 9 October 2022
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Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license
(https://creativecommons.org/license
s/by/4.0/).
Sustainability 2022, 14, 12844 2 of 41
Manipulating nano-, pico-, or femtoliter volumes of fluids [15], microchannels serve
as electronics, sensors, valves, pipes, and other structures [16,18]. These structures
integrated into systems can perform analyses (or other laboratory processes) on a chip
called a “lab-on-a-chip” in the range of millimetric dimensions [15,16].
The current trend in sensor technologies is to develop labs-on-chips that allow, for
example, the diagnosis of diseases in a very short time, or testing/monitoring (medical
diagnostics [19], food, environmental monitoring, etc. [20,21]) in the field (i.e., point-of-
need/care) [20,22] outside of central laboratories with devices that are affordable and
easy to use by anyone, anywhere, and at any time.
Microfluidic devicesalone or integrated in sensorshave become increasingly
important tools for the control of pollution levels in air, water, or soil. One of the
important advantages of using advanced materials and/or technologiessuch as
microfluidic devices integrated in biosensorsis the continuous and real-time
monitoring of environmental contaminants such as toxic heavy metal ions, organic
contaminants (e.g., phenols/phenolic compounds, pesticides/insecticides), pathogenic
microorganisms, or gas pollutants [23,24] for a sustainable environment.
This review paper presents the most common and newest materials used in the
fabrication of microfluidic devices integrated in sensors and biosensors, their advantages
and disadvantages, and the standard and new detection methods for microfluidic
environmental analysis of organic contaminants, pathogenic microorganisms, and toxic
heavy metal ions.
2. Environmental Pollution: Pollution Types and Potential Solutions for Their Reduc-
tion/Sustainable Management
As is known, there are three major types of pollutants that cause degradation of the
natural environment, namely, water, soil, and air pollutants. Of the gaseous or air
pollutants, the most common are CO, CO2, NO2, SO2, H2S, and volatile organic
compoundsthose that are released directly into the atmosphere and affect both the
environment and the health of people and/or animals [2527].
Domestic or industrial waste pollutes water and soils with heavy metals,
hydrocarbons, inorganic and organic solvents, plastics, etc. [2830]. A first step in order
to solve the problems related to pollution is the development of new technologies and
economical approaches for the continuous monitoring of pollution sources; removing
polluting factors; establishing strategies to protect the atmosphere, continental or
maritime waters, and soils; and/or increasing the efficiency of using natural resources in
accordance with the actual legislationfor example, implementation of Agenda 2030 for
Sustainable Development [3,17].
One of the novel developments in advanced materials and technologies is the use of
microfluidic and lab-on-a-chip devices for pollution analysis. Microfluidic devices and
microfluidics-integrated sensors represent powerful analytical tools for the real-time and
in situ detection of different types of micropollutants present in aquatic systems, with
high sensitivity and specificity [30].
The applications of microfluidic devices for the detection of the most common
pollutants are presented schematically in Figure 1.
Sustainability 2022, 14, 12844 3 of 41
Figure 1. The environmental applications of microfluidic devices for the detection of the most
common pollutants.
In the following sections, the most common and newest materials used in the
design and fabrication of microfluidic devices, microfluidic detection systems, and
microfluidics-integrated (bio)sensors for pollution analysis, along with their advantages
and disadvantages, are presented. Furthermore, we synthesized and evaluated the old
and new microfluidic detection systems for the environmental analysis of heavy metals,
phenolic compounds, pathogens, nitrites, nitrates, and ammonia.
3. Design and Fabrication of Microfluidic Devices
3.1. Component Materials for Microfluidic Devices
Microfluidic chips are fabricated using the following materials: (a) inorganic
materials, such as glass, silicon, ceramic microfluidic chips, and transition metal carbides
and/or nitrides; (b) polymeric materials, e.g., polydimethylsiloxane (PDMS) [15] and
thermoset polyester (TPE) as elastomers, and polystyrene (PS), polymethylmethacrylate
(PMMA), polycarbonate (PC), etc., as thermoplastic polymers and hydrogels, which are
relatively novel polymers; and (c) paper-based microfluidic chips [15]. In Table 1, the
component materials for microfluidic devices, along with their main characteristics
(including advantages and drawbacks) and principal fabrication methods, are briefly
presented [15,3138].
Sustainability 2022, 14, 12844 4 of 41
Table 1. Material types, characteristics, and fabrication methods for microfluidic chips.
Material Types
Characteristics
Fabrication Methods
Silicon
(or silicon-based substrates)
(i) Resistant to organic solvents;
(ii) Ease in depositing metals;
(iii) High thermal conductivity [39];
(iv) Stable electroosmotic mobility;
(v) High elastic modulus (130 to 180 GPa);
(vi) The precise definition of nanoscale channels or pores;
(vii) Transparent to infrared [35];
(viii) Chemical stability [40].
Drawbacks: (ix) Difficulties in handling them (they are
hard), making it difficult to make valves and/or pumps, or
active microfluidic components in general; (ix) high costs
[34]
(a) Wet (chemical) etching [34,35,4042];
(b) Dry etching [43];
(c) Powder blasting [33];
(d) Micro-hot embossing molding [44];
(e) Photolithography [33]
Glass (or glass-based sub-
strates)
(i) Optically transparent;
(ii) Electrically insulating (amorphous);
(iii) Compatible with biological samples;
(iv) Not permeable to gas;
(v) Has a low (relative) non-specific adsorption.
Drawbacks: (vi) Vertical walls are more difficult to etch
than Si;
(vii) Production is time-consuming and expensive [36]
(a) Wet or dry (chemical) etching [35];
(b) Metal or chemical vapor deposition [35];
(c) Patterning and cutting [45];
(d) Photolithographic patterning [46];
(e) Thermal bonding [41];
(f) Molding process [47];
(g) Powder blasting
Al-oxide-based materials
(i) Low-temperature co-fired ceramic (LTCC);
(ii) LTCC compared to other technologies allows the
integration of heaters, sensors, and electronics (control
and measurement electronics, and a light-detection sys-
tem) into a single module; thus, the measurement system
can be simplified;
(iii) Thick film materials offer the possibility to fabricate
not only the networks of conducting paths in a single
package, but also other microsystems, electronic compo-
nents, and sensors [35].
Drawback: No mechanical flexibility
(a) Laminate sheets of Al-oxide-based material are pat-
terned, assembled, and heated at elevated temperatures
[48];
(b) Electrodes can be deposited onto LTCC using expan-
sion-matched metal pastes [35]
Transition metal carbides
and/or nitrides and Mn+1Xn
(MXenes)
(i) High intercalation capacity;
(ii) High metallic conductivity [49];
(iii) Large surface area;
(iv) Good ion-transport properties;
(v) Low diffusion barrier;
(vi) Biocompatibility;
(vii) Hydrophilicity;
(viii) Ease of surface functionalization [50];
(ix) Higher signal-to-noise ratio in electrochemical sensing
[51]
(a) Wet chemical etching [50];
(b) Selective etching and exfoliation process [49];
(c) Chemical vapor deposition (CVD) growth [52]
Polydimethylsiloxane (PDMS)
(i) Optical transparency up to 280 nm;
(ii) Ductile (flexible )material;
(iii) Elasticity (which can be “adjusted” using crosslinking
agents);
(iv) Biocompatibility;
(v) Sealing capacity of materials such as glass, polysty-
rene, and PMMA [15];
(vi) Does not require a clean room [15];
(vii) Permeability to gases (is more permeable to CO2 than
to O2 or N2) and water vapor;
(viii) High thermal stability up to T = 300 °C;
(ix) Cost-effective production at micro scale.
Drawbacks: (x) Low shear modulus (e.g., cannot be used
at for high-frequency droplet generation at high operating
pressure [51];
(xi) Swelling in organic solvents;
(xiii) Diffusivity [15,32,33]
(a) Device molds made through conventional machining;
(b) Device molds made by photolithographic methods
[53];
(c) Micromoldingcasting process (liquid PDMS prepoly-
mer is thermally cured at mild temperatures of 4080 °C
and can be cast at nanometer resolution from photoresist
templates [33,53] or other techniques;
(d) “Microwire molding” [15,32];
(e) Rapid prototyping [54]
Thermoset polyester (-TPE)
(i) Insoluble;
(ii) Highly resistant to creep;
(iii) Optically transparent and absorbs UV light [55];
(a) Polymerization of polyester and styrene through UV or
heat [35];
(b) Photolithography [58];
Sustainability 2022, 14, 12844 5 of 41
(iv) Inexpensive;
(v) Higher elastic modulus (1-100 MPa) than PDMS [56].
Drawbacks: (vi) High stiffness (improper for the fabrica-
tion of valves);
(vii) High cost;
(viii) Hydrophobic [35,57]
(c) Replica molding [59]
Polystyrene (PS)
(i) Optically transparent;
(ii) Biocompatible,
(iii) Inert;
(iv) Rigid,
(v) Relatively hard and brittle;
(vi) Good electrical properties;
(vii) Surface can be easily functionalized;
(viii) Excellent gamma radiation resistance [60].
Drawbacks: (vii) Difficulties encountered in the thermal
bonding step [33];
(viii) Hydrophobic (requires chemical modification of
styrene PS surface or plasma oxidation to become hydro-
philic) [61]
(a) Injection molding [62];
(b) Hot embossing [35];
(c) Prototyping by UV laser photoablation [38]
Polymethylmethacrylate
(PMMA or PMMA substrate)
(i) Low cost [63];
(ii) Rigid mechanical properties;
(iii) Excellent optical transparency;
(iv) Compatibility with electrophoresis [37];
(v) Biological compatibility [35];
(vi) Elastic modulus of 3.3 GPa [35];
(vii) Gas impermeability;
(viii) Micromachining at 100 °C [35].
Drawback: The cost of PMMA substrate per unit area is
high [58]
(a) Hot embossing [63];
(b) Solvent imprinting;
(c) Atmospheric pressure molding [64]; and thermal bond-
ing;
(d) Injection molding [62];
(e) Laser ablation [65];
(f) CO2 laser micromachining [66];
(g) Plasma etching [37];
(h) Nanoimprinting
Polycarbonate (PC)
(i) Good machining properties;
(ii) High impact resistance;
(iii) Enhanced chemical resistance;
(iv) Low water absorptivity (<0.01%);
(v) Good electrical insulating properties;
(vi) Long-term stability of surface treatments;
(vii) Extremely low absorption of impurities;
(viii) Low cost;
(ix) Durable material;
(x) Very high softening temperature (~145 °C) [35].
Drawback: (xi) Low transparency in the visible and near-
UV spectra
(a) Prototyping by UV laser photoablation [38];
(b) Hot embossing [67];
(c) CO2 laser machining [68];
(d) Injection molding [62];
Polyethylene terephthalate
(PET)
(i) Resistant to thermal shock in comparison with silicon-
based substrates [40];
(ii) Inexpensive production [40]
Laser ablation [69]
Cyclic olefin copolymer
(COC)
(i) Optical transparency in the visible and near-UV spec-
tra; enhanced chemical resistance;
(ii) Good electrical insulating properties;
(iii) Low water absorptivity (<0.01%);
(iv) Extremely low level of impurities;
(v) Long-term stability of surface treatments [70]
(a) Micromilling method [71];
(b) Photolithography [72,73]
Hydrogel
(i) Extremely hydrophilic polymer [74];
(ii) High biocompatibility;
(iii) High biodegradability.
Drawbacks: (iv) Softness of hydrogels;
(v) Silk fibroin, collagen, and gelatin have poor processa-
bility;
(vi) Complex microfluidic networks cannot be created
only simple or 2D ones;
(vii) Channel deformation [74]
(a) Photopatterning [75];
(b) Injection molding [76];
(c) Coaxial extrusion-based 3D printing [77]
Paper
(i) Easy to work with;
(ii) Can be treated to chemically bind molecules or pro-
teins;
(iii) Compatible with biological samples;
(iv) Inexpensive material.
(a) Paper patterning;
(b) Photolithography [78];
(c) Screen printing [79];
(d) Inkjet printing [80];
(e) Plasma oxidation;
Sustainability 2022, 14, 12844 6 of 41
Drawback: (v) Difficult to distinguish individual channels
on the chip [35]
(f) Roll-to roll;
(g) Cutting [81,82] and ink-writing [83];
(h) Wax printing [83]
In general, materials used for substrates include glass, ceramics, and silicon. When
it is necessary to obtain flexible disposable sensorsfor example, in rapid test surgery
plastic sheets made from polyamide, polycarbonate, and polyester can be used.
The physicochemical and mechanical properties of glass/silicon-based microfluidics
materials depend on the type of glass, and the most important properties required for
them are transparency, solvent compatibility, Young’s modulus, rigidity, and operating
temperature. In Figure 2, the main characteristics of glass/silicon-based microfluidics are
schematically presented.
The transparency of borosilicate glass, alkali-free glass and ultrathin glass is in the
range of 330-2500 nm in wavelength, while for quartz or fused silica the transparency is
in the range of 200 to 3500 nm [84]. In contrast with glass, which is optically transparent,
silicon is opaque [33].
Sustainability 2022, 14, 12844 7 of 41
Figure 2. The main characteristics of commonly used materials for microfluidic device fabrication:
(a) glass/silicon-based materials; (b) polymer-based materials. PDMSpolydimethylsiloxane,
PSpolystyrene, PCpolycarbonate, PMMApolymethylmethacrylate, TPEthermoset polyes-
ter;
.
The highest operating temperature for quartz and fused silica is 1500 °C. Silicon
and glass are resistant to most organic solvents, with the following exceptions: glass has
no solvent compatibility with HF, and silica has no compatibility with KOH [84], [33].
The silicon/glass-based materials for microfluidic device fabrication also have a
very stable surface charge, limited 3D channel profile, and the possibility to achieve the
smallest channel at the nano level. For instance, the smallest (16 nm deep glass
nanochannels) were reported by Pinti et al. [85], who fabricated chemically uniform
nanochannel networks with an ultralow aspect ratio in borosilicate glass substrates,
designed to perform multiple unit operations on a single chip. For electrodes, any noble
metals used for conventional macroscopic electrodes can be adapted [86].
The new ceramic materials used as components of microfluidic devices include
transition metal carbides and/or nitrides, and Mn+1Xn (MXenes) [49,50], which are
characterized by high metallic conductivity, large surface area, good ion-transport
properties, a low diffusion barrier, biocompatibility, and ease of surface
functionalization [50].
The polymer-based microfluidic materials are the most used materials for the
fabrication of microfluidic chips, because of the specific characteristics presented
succinctly in Table 1 and Figure 2b, such as optical transparency (PDMS, TPE, PS, COC),
flexible materials (PDMS), biocompatibility (PDMS, PMMA, PS), etc. Among them,
hydrogels have specific characteristics enabling them to mimic natural mechanical and
structural cues for cell adhesion, proliferation, and differentiation [87]. Moreover,
hydrogel materials are used to construct complicated and large-scale tissues with high
cell density, high metabolic requirements, and intricate architectures [74]. Despite the
specific characteristics of hydrogelssuch as extreme hydrophilicity [74], high
biocompatibility, and high biodegradabilityhydrogels are not frequently used as
fabrication materials, because maintaining the device’s integrity is quite challenging and
can limit their use in the long term.
Another important material used in microfluidic devices is paper. Paper represents
a highly useful supporting material for developing sensing devices due to its various
advantages, such as low cost (200 times less expensive than PET and 1000 times less
expensive than glass) [80], ease of printing, high hydroscopic properties, and
biodegradability. There are different types of paper used as substrates in the
manufacture of microfluidic devices, such as (i) Whatman chromatography paper,
characterized by being hydrophilic, reproducible, and homogeneous, with a clean
surface, uniform thickness, wicking properties, medium retention, medium flow rate,
and biocompatibility; (ii) glossy paper, characterized by being transparent, degradable,
and easy to chemically modify; (iii) nitrocellulose (NC) membranes with specific
characteristics including a microporous polymeric surface, high binding capacity for
biomolecules, combustibility in air, stability, and reproducibility; (iv) paper towels
(translucent and permeable); and (v) ITW TechniCloth wipers (composed of cellulose
and polyester) [80].
3.2. Microchip Fabrication
Microfluidic devices can be fabricated using different techniques that include
prototyping techniques, such as replica molding [15,32], rapid prototyping [15,36], soft
lithography [15,86,8890], injection molding [15,37], and hot embossing [15,33,35]. Other
fabrication techniques include X-ray lithography [15,62,89,91], photolithography/optical
lithography [15,88,92] or photolithography followed by etching and bonding [15,89], and
Sustainability 2022, 14, 12844 8 of 41
direct fabrication techniques such as laser photoablation or laser micromachining
[15,30,37,38,69]. In Table 2, the advantages/disadvantages of different fabrication
methods used for microchip fabrication are presented.
Table 2. The advantages/disadvantages of different methods used for microchip fabrication.
Fabrication
Methods
Material
Advantages
Disadvantages
Ref.
Soft lithography
PDMS
High resolution (down to a few nm);
real-time detection; portable;
disposable; cost-effective; able to
fabricate 3D geometries
Requiring high sample
concentration; pattern
deformation; vulnera-
ble to defects
[90,93]
Hot embossing
PMMA
Cost-effective, precise, and rapid
replication of microstructures; mass
production
Restricted to thermo-
plastics; difficult to
fabricate complex 3D
structures
[94]
Injection molding
Thermoplastic polymers
Easy to fabricate complex geometry,
fine features, and 3D geometries;
low cycle time; mass production;
highly automated
Restricted to thermo-
plastics; high-cost
molds; difficult to form
large undercut geome-
tries
[62]
Laser photoablation
PET
Rapid; large-scale production
Multiple treatment
sessions; limited mate-
rials
[30,69]
Conventional
photolithography/
optical
lithography
Polymers
High wafer throughputs; ideal for
microscale features
Usually requires a flat
surface to start with;
requires chemical post-
treatment
[92]
Photolithography
PDMS
Portability;
cost-effective and high automation;
high sensitivity
Low throughput
[95]
Electron-beam
lithography
SU-8 3010
Good resolution; can be precisely
aligned
Expensive;
requires more time to
fabricate
[96]
X-ray lithography
PMMA
High resolution to fabricate nano-
patterns; absorption without spuri-
ous scattering; able to produce
straight, smooth walls
Difficulties in master
fabrication process;
time-consuming; high
cost
[91]
Photolithography and
complex pattern
Whatman No.1 chroma-
tography paper, ITW
TechniCloth, and Scott
hard roll paper towels
Mass production; good stability
Expensive equipment;
toxic reagents; fragile
when bending
[80]
Photolithography or
wax printing
SU-8
Simple; portable; fast;
low cost
-
[97,98]
Wax printing
Whatman No.1 chroma-
tography,
Whatman filter paper,
and nitrocellulose (NC)
membranes
Simple and fast to fabricate; mass
production
Low resolution; not
resistant to high tem-
peratures
[99,100];
Inkjet printing
Filter paper
Cheap reagents; mass production;
compatible with multiple functional
inks
Requires an improved
ink jet printer; low
speed
[101]
Sustainability 2022, 14, 12844 9 of 41
Inkjet etching
Filter paper
Cheap reagents; prints flexible, fold-
able channels at 100 cm2 in size
Low resolution; low
production; not suitable
for complex patterns
[101,102]
Screen printing
Whatman No.1 filter
paper
Low cost; mass production; multiple
functional inks
Low resolution; differ-
ent patterns need dif-
ferent printing wire
[79]
Nanoimprinting
PMMA
Cost-effective; high sensitivity;
high resolution; precise control
Expensive;
low throughput
[103]
4. Microfluidic Detection Systems and Microfluidics-Integrated (Bio)Sensors for Pol-
lution Analysis
4.1. Sensor Types and Their Required Characteristics for the Detection and Monitoring of Envi-
ronmental Contaminants
Sensors are devices that can analyze the target analyte quantitatively based on the
interaction between the recognition element and the target samples. There is a wide
range of sensing devices, classified depending on the detection mode and their
measurable properties, such as bio(chemical) [19], electrochemical [30], piezoelectric
[104], optical [28], thermal [30,105], magnetic [106], or magneto-optical sensors that
provide critical analytical information in many fields [40,107], as illustrated
schematically in Figure 3. These types of sensors are able to recognize the analyte of
interest on the surface of a signal transducer, depending on the chemical, electrical,
optical, magneto-optical, or thermal signal acquisition.
Among them, biosensors are analytical devices that consist of (i) a bioreceptor (i.e.,
a biological recognition component), (ii) a physicochemical transducer to generate a
measurable signal, and (iii) an element for signal amplification and processing [108,109].
Biosensors can be classified into nucleic-acid-based biosensors, antigen-based
biosensors, or antibody-based biosensors, depending on the biological molecule (i.e.,
nucleic acids, antigens, or antibodies).
The optical and electrochemical biosensors have been successfully used in
biological, chemical, and biomedical analysis, in the detection of biological targets
[21,88], in cell culture studies [32], in environmental analysis/monitoring [20,21,110,111],
in food analysis [112] and control [110], and in drug discovery and delivery [110].
Figure 3. Classification of sensors depending on the detection mode and their measurable proper-
ties.
Optical biosensors consist primarily of (i) a light source, (ii) optical components
used to generate and focus the light beam to a modulating agent, respectively, (iii) a
modified detection (sensing) head, and (iv) a photodetector [30,113]. Energy,
Sustainability 2022, 14, 12844 10 of 41
polarization, absorption, fluorescence, light scattering, amplitude, decay time, and/or
phase [114] are different parameters that can be used in the optical detection of targets.
An electrochemical (bio)sensor consists of (a) a receptor that recognizes the species
to detect it with high specificity and selectivity, and (b) a transducer that translates the
event of recognition into a measurable physical (i.e., electrical) signal [115]. The
electrochemical devices used as sensors present the most promising advantages in
comparison with various classes of elements able to transduce a chemical or biochemical
event into a measurable signal, or in comparison with the conventional methods.
Among the most important advantages of the electrochemical devices used as
sensors are their flexibility, ability to perform analysis in a short time, low fabrication
costs, and ease of implementation and disposability (i.e., easy-to-use sensing devices)
due to miniaturization of the electrochemical systems by coupling microfluidics with
electrochemical detection analysis [111]. However, the challenge relates to the
fabrication of the miniaturized electrochemical systems due to the thick electrodes that
have to be integrated within the microfluidic microelectromechanical systems (MEMSs)
and nanoelectromechanical systems (NEMSs) [110]. In both MEMS and NEMS devices,
the electrodes used in the electrochemical measurements have dimensions in the
micrometric range, in comparison with the traditional electrochemical analysis devices,
which are of millimeters in size. The micro- and nanoelectrodes offer the following
advantages: measurement of small currents at pico- and nanoampere levels, rapid
response to changes in applied potential, low ohmic reduction in electric potential,
efficient diffusional mass transport (at microliter sample volumes), and steady-state
response to diffusion-controlled potential [21].
Electrochemistry has been and still is used to study the heterogeneous kinetics of
electron transfer at the metalsolution interface [21]. Electrochemical phenomena are
measured using a three-electrode cell consisting of (1) a working electrode (WE) where
redox reactions occur, (2) a counter electrode (CE) that is controlled by the potentiostat
to set the potential of WE and the equilibrium current, and (3) a reference electrode (RE)
that provides a response to the WE potential to the potentiostat [21,111]. The WE and CE
are immersed in the solution being studied, and the RE is often in indirect electrical
contact with the help of a conductive salt bridge [21,111]. Recently, miniaturized
electrochemical biosensors have shown the advantages of real-time monitoring and
label-free detection of biomarkers [116].
The piezoelectric materials used in sensors determine the mechanical resonance of
the vibrating crystal at its natural frequency. As the analyte of interested is exposed to
the sensing material, a reaction will eventually occur and produce a shift in the
frequency that causes a change in the electrical signal. The research of piezoelectric
biosensors integrated with microfluidics is quite underdeveloped so far. Possible
reasons could include their low sensitivity, poor biocompatibility, and complicated
fabrication [17].
Several characteristics of sensors can be obtained to determine the response
capability and performance. The optimization of these characteristics is critical to
assessing the performance of the sensors.
The main parameters that determine the quality of biosensing are selectivity,
sensitivity, and linearity. Figure 4 summarizes the key parameters in the evaluation of
biosensors’ performance.
Sustainability 2022, 14, 12844 11 of 41
Figure 4. Characteristics used for the evaluation of (bio)sensor performance.
Selectivity: Selectivity is the most critical feature of a biosensor (e.g., in case of
interaction of an antigen with the antibody) and requires special attention when
selecting the suitable bioreceptors [117]. The selection of a proper bioreceptor leads to
the detection of a specific bioanalyte in a sample containing other mixtures and
chemicals. The interaction model of an antigen with the antibody is one of the best
examples to describe the selectivity of bioreceptors. For instance, bioreceptors (e.g.,
antibodies) are immobilized on the surface of the transducer. When an antibody is
exposed to the surface, it will interact only with the antigens, leading to the successful
detection selectivity of the target biomolecule and better performance of the sensors or
nanobiosensors.
Sensitivity: In various medical and environmental applications, nanobiosensors are
needed to detect concentrations of the target analyte in samples as low as nanograms per
milliliter (ng/mL) or even femtograms per milliliter (fg/mL) [117]. It is known that
portable onsite biosensors, due to the open environment of analysis, affect (decrease) the
detection results. Conversely, through biosensors integrated with microfluidic devices,
because microfluidics provide a closed and stable biosensing environment, sensitivity is
improved and, as a result, the performance of the biosensor is enormously increased
[17].
Linearity: In biosensors and nanobiosenors, linearity or linear range (LR) is the
feature that measures the change in the range of the nanobiosensor’s response to the
bioanalyte concentrations linearly with the concentrations. Linearity is related to the
resolution of the (bio)sensors and nanosensors, where the detection of the smallest
change in the analyte concentration is required to measure the change in the
nanobiosensor’s response. From the instrumentation point of view, sensor fabrication
requires a linear response. Whether a linear or nonlinear response is obtained can be
determined based on the objectives of the fabricated devices. Even though the
observation of nonlinear responses leads to consistent, repeatable, and predictable
results, from the instrumentation point of view, a linear response is highly desirable in
the fabrication of sensors. In terms of sensor calibration, the linear region of the input
output values helps to perform the mathematical calibration for the unknown.
Therefore, the consistency in the linear variation of the sensor also determines the
stability of the device.
Sustainability 2022, 14, 12844 12 of 41
4.2. Miniaturization and Integration of Electrochemical Sensors in Microfluidic Systems
Typically, a microfluidic MEMS comprises a set of microchannels and
microelectrodes, in which the latter are designed based on a model that can control the
flow of a selective and sensitive fluid inside the microchannels. Essentially, two separate
substrates are required to obtain a functional microfluidic MEMS, where the
microchannels that are encompassed in the first substrate are sealed by bonding to the
second substrate where the microelectrodes are located [110]. The idea of combining
microchannels with electrochemical techniques has its roots in the early days of
microfluidics, when electrophoretic separations used microchannels for filtration
[21,40,86].
Electrochemical sensors are the most studied sensors [118], and they are typically
based on a redox reaction involving the target analyte in the electrolyte at the WE,
resulting in variation in the electrical signal [88,118]. When we measure the current and
the potential difference between electrodes, the method is called amperometry and
potentiometry, respectively. Potentiometry is usually used for ion-selective electrodes’
(ISEs) measurements (e.g., pH electrodes, other ISEs). One of the most used
electroanalytical methods is voltammetry or voltamperometry. This method is a subclass
of amperometry, which measures the current as the applied potential is varied [118].
Cyclic voltammetry is performed by applying an up-and-down linearly varying
potential between the WE and the RE, and then plotting the current generated externally
from the CE to the WE; the resulting curve is called a cyclic voltammogram or CV [118].
In electrochemical impedance spectroscopy (EIS), an alternating voltage is applied,
with a frequency that varies from 103 to 105 Hz, and the current is measured at the same
frequency [118]. The results are analyzed on a Nyquist diagram [118], with the
imaginary part as a function of the real part [88,118]. EIS is a powerful electrochemical
method that has recently become popular in biosensitivity due to its ability to detect
binding events on a transducer’s surface. In EIS, a DC potential (EDC) and a small
sinusoidal AC perturbation (EAC, B510 mV amplitude) are applied between the WE
and the RE. The magnitude and the phase angle (θ) of the resulting current (I) are
recorded as a function of the AC frequency [21]. EIS facilitates the extraction of device-
specific parameters from an equivalent circuit model, and these parameters are used to
describe the performance of the microelectrodes in a microfluidic channel [119]. Thus,
stable Ag/AgCl microelectrodes, manufactured using a combination of
photolithographic and electroplating techniques, have been shown to be useful for
electrochemical analysis in microfluidic systems [119].
4.2.1. Microelectrode Materials Used in Electrochemical Device Sensors
One of the most important factors in designing an electrochemical sensor is the
choice of material for the WE. The electrodes must be suitable for the specific application
(i.e., chemically resistant to the sample, chemically stable over time, etc.) and have
specific characteristics such as sensitivity, selectivity, or long-term stability. The most
used materials for electrodes with applications as sensors are (i) carbon-based materials
(e.g., screen-printed carbon electrodes, carbon fibers, diamond, etc.) [120]; (ii) metallic
electrodes, such as Au [121], Pt [86], Pd [122], Cu [123], Ni [124], Hg/Au amalgams, or Bi;
and (iii) semiconductor metal oxides [20,40].
For different electrochemical applications, using activated charcoal, magnesium, or
melanin, there has recently a great interest in producing biodegradable and compostable
electrodes [20]. Carbon electrodes are used in electrochemical detection because (i) the
fouling is minimal [40], (ii) the potential range for organic compounds is larger than that
of metal electrodes [40], and (iii) they use low-noise metal microwires (less than 50 m)
as the working electrodes for electrochemical detection using platinum, gold, and
copper [121]. Wang et al. [122] demonstrated that a Pd electrode had better detection
sensitivity for hydrazine than a carbon electrode in electrochemical sensors. They
Sustainability 2022, 14, 12844 13 of 41
showed that when the Pd electrode was used, the signal recorded presented sharp peaks
and an improved signal-to-noise ratio [40,121]. By using gold electrodes for the detection
of phenolic compounds (e.g., chlorophenols, aminophenols), the signal-to-noise ratio
was greatly improved, while the peaks became sharper compared to other electrodes.
Noble metal electrodes bring another advantage, namely, the electrocatalytic effect
[40,121]. By using Cu electrodes, sugars can be detected, while when using Ni as a
working electrode, electrocatalytic effects towards aliphatic alcohols and sugars have
been demonstrated [40,124].
Electrodes made of Hg/Au amalgams have the required electrochemical properties
to detect nitroaromatic explosives [40,125], while electrodes made of Bi show similar
electrochemical properties to carbon electrodes, with a similar signal-to-noise response
[40,125].
4.2.2. Microelectrodes Fabricated for Use in Microfluidic Detection Systems and Micro-
fluidics-Integrated (Bio)Sensors
The development of electrochemical sensors uses certain design criteria, such as (i)
miniaturized manufacturing design [111], (ii) sensitivity and selectivity [111], (iii)
robustness, (iv) reversibility, (v) speed, (vi) automation, (vii) reliability, (viii) stability,
(ix) data acquisition, (x) compound analysis capabilities, (xi) low power consumption,
and (xii) overall cost [35,111]. The innovative techniques used for making microfluidic
electrochemical devices used as sensors include thick- and thin-film technology
(metallization) [111], chemical etching, and photolithography. Using these methods,
two-dimensional sensors have been fabricated [88].
The most used methods are wet or dry chemical etching in combination with the
pattering of photoresistors. The steps involved in forming thin-film metal electrode
patterns by chemical etching are (i) deposition of a metal layer, (ii) spin-coating of a
photoresistor and pre-baking, (iii) exposure to UV light and development, (iv) rinsing of
the photoresistor, (v) etching of the metal layer, and (vi) removal of the photoresistor
[86,119].
The steps involved in forming thin-film metal electrode patterns by lift-off
techniques are (i) spin-coating of a photoresistor and pre-baking, (ii) exposure to UV
light, (iii) soaking in an aromatic solvent and development, (iv) rinsing of the
photoresistor after baking, (v) deposition of a metal layer, and (vi) removal of the
photoresistor. The lift-off technique has been used for patterns of noble metals (i.e., Pt
and Ir) [86].
The fabrication of pumps, valves, and other microfluidic components is contingent
on bulk micromachining to create microscopic 3D structures in a silicon substrate
[86,88]. For 3D structures, some researchers [89,126] have applied field-assisted bonding
or anodic bonding techniques that consist of sealing glassmetal, glasssemiconductor,
and glassglass systems [89,126]. They demonstrated that field-assisted glass sealing
offers a simple and rapid method of making reliable, strong hermetic bonds at low
temperatures [89,126]. The copper electrodes for conductivity detection can be fabricated
on a printed circuit board attached to a PDMS−glass device; Pd electrodes can be
fabricated on glass plates before bonding with PDMS for amperometric detection
[88,123].
Of the many techniques to fabricate microelectrodes for use as sensing devices,
electrochemical deposition has recently been progressively used for generating thick
electrodes integrated within microfluidic MEMSs [119,127]. In addition, electrochemical
deposition offers a simple procedure for the manufacture of microelectrodes that are
made of different types of metals [119,127]. The electrodeposition of nanocrystalline
metals and alloys has been investigated by many researchers [127].
From a nanostructure point of view, electrochemical deposition is used in order to
obtain laminar metal coatings and freestanding foils, in a single bath or between two
baths, by the alternating movement of the growing electrode (an alternative sequence of
Sustainability 2022, 14, 12844 14 of 41
two different metals) [127]. It has been observed that due to the dynamic characteristics
of the electrokinetic process, spontaneous formation of multilayers often occurs via
electrodeposition of different nanometric materials, such as Fe-Ni, Zn-Ni, Cu-Sb, or Au-
Cu [127]. Gold electrode bases for amperometric biosensors were first prepared on
polycarbonate sheets using a photodirected selective electroless gold plating technique
[121,128].
Wang et al. [128] prepared a micro-gold-film electrode based on a polycarbonate
(PC) coating sheet with a photodirected electroless plating technique. This developed
micro-flow-injection biosensor system with PC could successfully be applied for the
determination of glucose content in pharmaceutical injections [128]. For environmental
monitoring applications, Wang et al. [129] used Si-based techniques to create an
electrochemical sensor for the detection of trace metals in natural waters, and achieved
remarkable sensitivity (detection of trace Ni and U required only 5 and 20 min,
respectively). In their experiments [129], the integrated membrane/electrochemical
sampling sensor pursued trace monitoring of uranium and nickel using propyl gallate
(PG) and dimethylglyoxime (DMG) as chelating agents. These tests established
adsorptive stripping protocols for trace uranium and nickel based on complexation with
PG and DMG. Experimental variables including reagent delivery rate and ligand
concentration were used to characterize and test the experimental stripping probe.
Despite internal dilution, the renewable-flow probe resulted in extremely low detection
limits, such as 0.9 μg/L (1.5 × 108 M) for nickel and 10 μg/L (4.2×10-8 M) for uranium
[111,129].
4.3. Miniaturization and Integration of Optical Sensors in Microfluidic Systems
The microfluidics integrated in optical sensors are also known as optofluidics. By
integrating the optical sensors in a microfluidic system, sample processing and
biosensing reactions are performed in a closed and relatively stable environment that
allows for fast, high-efficiency, contactless analysis under a well-controlled
microenvironment. Other advantages include a low detection limit, versatility, being
label-free and non-destructive, and their ability to detect a wide variety of analytes or
multiple analytes at the same time with fast signal monitoring and analysis [16,30,71].
Moreover, the simple design of optofluidic systems allows for reducing the cost of the
device fabrication as well as precise quantification and detection of different
environmental pollutants, including heavy metal ions, pesticide residues in agricultural
foods, herbicides, food allergens, phenolic compounds, pathogens, etc. [130132].
4.4. Microfluidic Detection Systems for Pollution Analysis
Microfluidics can be coupled with a multitude of detection devices for optical
detection, electrochemical detection, mass spectrometry, etc. In the case of optical
detection, the most common methods for microfluidics are (a) absorbance-based
detection, such as colorimetry [71,133,134]; (b) fluorescence detection [135,136]; (c)
chemiluminescence detection [137] or bioluminescence [138]; (d) surface plasmon
resonance (SPR), with or without fiber optics [139]; and (e) laser-induced fluorescence
(LIF) [140].
Colorimetric and fluorimetric detection schemes are well suited for the detection of
environmental contaminants in less accessible and remote areas. These methods require
only simple equipment, such as a light-emitting diode for excitation used in conjunction
with a photomultiplier tube or even a smartphone camera for detection [141]. In
addition, fluorescence detection is widely used due to its high selectivity and sensitivity
[142].
Due to its instrumental simplicity, availability, flexibility, rapid analysis with high
accuracy, low manufacturing costs, and facile implementation, microfluidic devices
coupled with electrochemical detection are more advantageous compared to traditional
electrochemical detection systems [100]. The main electrochemical detection methods for
Sustainability 2022, 14, 12844 15 of 41
microfluidics applied for the detection and monitoring of environmental contaminants
are (a) (chrono)amperometry [143]; (b) voltammetry, such as square-wave anodic
stripping voltammetry (SWASV) [72,73], differential pulse anodic stripping
voltammetry (DPASV) [144], cyclic voltammetry (CV) [30], or linear sweep voltammetry
(LSV) [145]; (c) conductometry [30,146]; (d) potentiometry [147]; and (e) electrochemical
impedance spectroscopy [148].
The voltammetric detection implemented in microfluidic devices, compared to
stationary analysis, is associated with improved detection limits, where the faradic
current increases due to the increased transport rate of the analyte to the electrode
surface [147] for microfluidic applications.
Contactless conductivity is one the most important techniques to detect inorganic or
small organic ions in electrophoresis. It is preferred due to the electrodes’ fouling,
bubble formation due to water electrolysis, and interference with high voltages used to
drive electroosmotic flow [149,150]. Conductivity detection can be achieved either by a
direct contact of the mixture with the sensing parts or by a contactless method where the
sensing electrodes are not attached directly to the measured mixture. This process
requires a detector cell as a basic part of the electronic circuitry. To evaluate the
performance of the contactless conductivity detection, two major issues need to be
addressed: the noise analysis, and the detector’s sensitivity.
4.4.1. Microfluidic Detection Systems for Heavy Metals
Over time, researchers have been concerned with the detection and monitoring of
heavy metal ions using different types of microfluidic systems or microfluidic sensors,
which allow continuous and on-site measurements of heavy metals.
Several optical methods are widely used to identify and quantify heavy metals,
including colorimetry [30], surface plasmon resonance, [71,139], fluorescence [30], and
chemi/bio luminescence [98,137,138]. Polymer-based optical microfluidic chips for the
analysis of heavy metal ions can be made from polymethylmethacrylate (PMMA), cyclic
olefin copolymer (COC)an amorphous polymerPDMS [142], or
polytetrafluoroethylene (PTFE)/perfluoroalkoxy alkane (PFA) tubes [71]. Figure 5 shows
the design and construction of a microfluidic platform with COC support (Figure 5a)
and a microfluidic chip molded in PDMS and fixed on glass substrate with connected
fibers and tubing for the continuous monitoring of Hg(II) (Figure 5b).
Sustainability 2022, 14, 12844 16 of 41
Figure 5. The construction of polymer-based optical microfluidic chips for the analysis of heavy
metal ions: (a) schematic representation of the microfluidic platform with cyclic olefin copolymer
support for the continuous monitoring of Hg(II); (b) schematic representation of the SU8 mold of
the optical chamber.
The detection method of the microfluidic optical system with gold nanoparticles
developed by Gomez and collaborators [71] is based on the selective recognition of
mercury by a thiourea derivative specifically designed and synthesized for the
continuous monitoring of Hg(II). The results obtained using this optofluidic system
showed improved analytical characteristics compared to the batch experiments, such as
a lower detection limit (11 ppb), higher sensitivity, and faster analysis time, all via an
easy, automatic, and low-cost procedure [71]. Mohan et al. [139] also reported the
design, fabrication, and characterization of an optical fiber sensor by cascading two
channels in a single fiber-optic probe using the SPR technique and ion-imprinted
nanoparticles for the simultaneous determination of lead (Pb) and copper (Cu) ions in
aqueous samples. The sensing of Pb(II) and Cu(II) ions is based on the interaction of ions
with corresponding ion-imprinted nanoparticles. When the solution of the metal ions
comes near the ion-imprinted nanoparticle layer, metal ions bind non-covalently with
the corresponding complementary binding sites and cause a change in the effective
refractive index of the sensing layer (i.e., ion-imprinted nanoparticle layer). The change
in the effective refractive index causes a shift in the peak absorbance wavelength of the
recorded spectrum. The experimental results showed that the detection limits of both
channels were the lowest in comparison with other studies reported in the literature on
sensing Pb(II) and Cu(II) ions.
A rapid, eco-friendly, and affordable method for detecting arsenic in water samples
was reported by Chauhan et al. [133]. Lace et al. [151] optimized a colorimetric method
based on leucomalachite green dye for its integration into a microfluidic detection
system. This method can be applied for monitoring wastewater as well as for the
detection of arsenic in areas with particularly high arsenic levels.
Table 3 presents a systematic overview of the microfluidic system types, detection
methods, fabrication of chips, and specific characteristics of the performance of the
optical sensors for different analytes, such as Cr(III) and Cr(IV), Ni(II), Cu(II), Hg(II),
Pb(II), Cd(II), and Fe(II).
Sustainability 2022, 14, 12844 17 of 41
Table 3. Optical microfluidic detection methods for various heavy metal ions.
Samples
Device Sub-
strate
(or Compo-
nents)
Detection Method
(and/or Mecha-
nism)
Fabrication Method
Analyte (Target)
Limit of Detection (LOD)
Linear Range (LR)
Ref.
Water sample
Chromatog-
raphy no. 1
paper
Colorimetry
Patterned paper
Cr(VI)
Ni(II)
Cu(II)
LOD for Cr(VI):
0.5 mg/L
LOD for Ni: 0.5 mg/L
LOD for Cu(II):
0.8 mg/L
[152]
Sample solution with the
addition of nanoparticles
(PtNP)
Glass-fiber
paper
Colorimetry
Printing technique
Hg(II)
LOD: 0.01 μM
[153]
Synthetic samples containing
Hg and aqueous NaOH solu-
tion (used to extract dithizone
from dithizoneCCl4 solution)
and then used as a chromogen-
ic reagent
Filter paper
Distance-based
colorimetry
Printing technique
Hg(II)
LOD: 0.93 μg/mL
[154]
Water sample; sample solution
of arsenic prepared in lemon
juice
Filter paper
Colorimetric micro-
detection
Simple pattern-
plotting method
As(III)
LOD: 0.01 mg /L
[133]
Environmental Samples from
(i) Bog Lake;
(ii) Killeshin water reservoir;
(iii) Laois groundwater;
(iv) Barrow Carlow River
--
Colorimetry (ab-
sorbance principle)
--
As(III)
LOD: 0.19 mg/L
LR: 0.073 mg/L
[151]
Natural water samples at the
sub-ppm range
Paper-based
device
Miniaturized chemi-
luminescence
Wax printing of
microfluidic paper-
based analytical
device (μPAD)
Cr(III)
LOD: 0.02 ppm
LR: 0.051.00 ppm
[98]
Seawater
Polymethyl-
methacrylate
(PMMA)
Colorimetry (ab-
sorbance principle)
Micromilling in
PMMA of micro-
channels
Fe(II)
Mn(II)
LOD for Fe(II):
27 nM
LOD for Mn(II): 28 nM
LR for Fe(II):
27200 nM
LR for Mn(II):
0.0286 M
[134]
Lyophilized (prepared with
bacterial luciferase and
NAD(P)H:FMN‐oxidoreductas
e) and mixed with aqueous
starch suspension
Polymethyl-
methacrylate
(PMMA)
Bioluminescence
Micromilling meth-
od
Cu(II)
LOD: 3 μM
[138]
Environmental water samples
Cyclic olefin
copolymeran
amorphous
polymer
Surface plasmon
resonance
Micromilling meth-
od
Hg(II)
LOD: 11 g/L
LR: 11100 g/L
[71]
Aqueous samples with mixed
concentrations of Pb(II) and
Cu(II) ions
Plastic-clad
silica (PCS) fiber
Fiber optics + sur-
face plasmon reso-
nance
Coating by thermal
evaporation of thick
copper and silver
film over unclad
cores of both chan-
nels (I and II); dip-
coating of non-
imprinted (NIP)
nanoparticles over
the films;
Cu(II)
Pb(II)
LOD for Cu(II): 8.18 x10-10
g/L
LOD for Pb(II): 4.06x10-12
g/L
LR: 4.061000 g/L
[139]
Aqueous sample solution and
aqueous M1 suspension
Polytetrafluoro-
ethylene (PTFE)
/perfluoroalkoxy
alkane (PFA)
tubes
Fluorescence
--
Hg(II)
LOD: 0.02 g/L
LR: 0.02200 g/L
[155]
Sustainability 2022, 14, 12844 18 of 41
Aqueous samples, sewage
waters
PDMS/glass
Fluorescence
--
Cd(II)
LOD: 0.45 g/L
LR: 1.1222.40 g/L
[137]
Natural water
Glass plates
Chemiluminescence
+ air sampling
Photolithography
and wet etching
Fe(II)
LOD: 3 x10-7 mol/L
LR: 1 x 10-6 to 5 x10-5 mol/L
[137]
Diluted stock solution of Fe(II)
with demineralized water
Glass
Optical detection
(absorbance princi-
ple)
Photolithographic
and wet-etching
techniques; photo-
resistant coating
Fe(II)
LOD: 1 M
LR: 1100 M
[156]
Water samples containing
certain concentrations of Pb
PDMS substrate
Fluorescence
Molded the chan-
nels in PDMS
Pb(II)
LOD: 5 ppb
[142]
There are many types of microfluidic systems for electrochemical detection,
including paper-based microfluidic systems (Whatman paper substrates with different
types of electrodes incorporated, e.g., boron-doped diamond paste electrodes) [100],
graphite as the WE [30,157159], polymer-based electrodes such as COC with silver and
bismuth as working electrodes, PMMA substrates with boron-doped diamond
electrodes [160], gold thin films [161], or PDMS/glass substrates and Au, Pt, etc., as WEs
[30].
For instance, Jung et al. [73] made a reusable polymer lab-on-a-chip sensor with a
microfabricated silver working electrode for detection using SWASV measurement of
lead ions in nature. One of the advantages of this polymeric COC-based microfluidic
sensor is its reusability. Thus, after 43 consecutive measurements, it was observed that
the peak potentials were stable and the dynamic response was in the range of
concentrations from 1 ppb to 1000 ppb [73]. The silver WE was microfabricated and
replaced, for instance, the conventional mercury and bismuth electrodes used for
SWASV detection by Zou et al. [72]. Gutiérrez-Capitán et al. [161] detected copper ions
in different electroactive samples of pollutants with a PMMA-based microfluidic system
and Au thin-film electrodes (Figure 6a,b). The copper ions were detected using anodic
stripping chronoamperometry (AS-CA) (deposition at −0.40 V and stripping at +0.05 V)
with a compact flow system including two electrochemical transducers integrated into a
miniaturized cell. Figures 6 and 7 present the components and the construction of
electrochemical microfluidic chips. Table 4 presents the microfluidic system types,
detection methods, fabrication methods of chips and working electrodes, and specific
characteristics of the performance of the sensors.
Figure 6. The construction of polymer-based electrochemical microfluidic chips for the analysis of
environmental pollutants (including heavy metal ions): (a) photo of the actual compact electro-
chemical flow system with PMMA substrate. (b) Schematic illustration of the Au thin-film elec-
trodes, where 1counter electrode (CE), 2working electrode (WE), and 3pseudo-reference
electrodes.
Sustainability 2022, 14, 12844 19 of 41
Figure 7. The construction of paper based electrochemical microfluidic chips for the analysis of
environmental pollutants (including heavy metal ions): (a) and (b) Boron Doped Diamond Paste
Electrodes (BDDPEs) design, (c) Schematic illustration of the µPAD (Whatman grade 1 chroma-
tography paper substrate with incorporated BDDPE), for the measurement of Pb and Cd Reprint-
ed with permission from Ref. [100]. Copyright (2017) American Chemical Society; (d) Illustration
of the microfluidic device based on paper (light blue) with graphite foil WE adapted after Ref.
[157] is licensed CC BY 4.0
Table 4. Electrochemical microfluidic detection methods for heavy metals.
Samples
Device Substrate
Working Elec-
trode (WE)
Type
Detection Meth-
od
Fabrication Meth-
od
Analyte
(Target)
Limit of Detection (LOD)
Linear Range (LR) and/or
Sensitivity
Ref.
Real samples of
gas-dissolved salty
soda water and
groundwater with
physical contami-
nation
Whatman filter
paper
Carbon
Square-wave
anodic stripping
voltammetry
(SWASV)
Screen-printed
carbon electrodes
(SPCE) on What-
man filter paper
Pb(II)
Cd(II)
LOD for Pb(II): 2 ppb
LOD for Cd(II): 2.3 ppb
LR for Pb(II) and Cd(II): 2
100 ppb
[158]
Rice flour
dissolved in meth-
anolwater
Whatman filter
paper
Boron-doped
diamond
(BDD)
Square-wave
anodic stripping
voltammetry
(SWASV)
Electrodeposition
of gold nano-
particles on boron-
doped diamond
(AuNP/BDD)
electrode
As(III) and
As(V)
LOD: 0.02 g/L
LR: 0.11.5 g/L
[159]
Aqueous solutions
Whatman grade 1
chromatography
paper or polyester
cellulose blend
paper
Bismuth plated
on carbon
Square-wave
anodic stripping
voltammetry
(SWASV)
Photolithography
or wax-printing of
microfluidic chan-
nels;
screen-printed
electrodes
Pb(II)
LOD: 1 ppb
LR: 5−100 ppb
Sensitivity: 0.17 μA (μg/L)1
[90]
Aqueous samples
(heavy metal stock
solutions);
mud-spiked sam-
ples
Whatman
filter paper grade 1
Graphite
Square-wave
voltammetry
(SWV)
Wax-printing of
microfluidic chan-
nels;
screen-printing of
electrodes
Cd(II) and
Pb( II)
LOD for Cd(II): 11 ppb; LOD
for Pb(II): 7 ppb
LR for Cd(II) and Pb(II):
10−100 ppb
Sensitivity for Cd(II): 0.015
μA (μg/L)1
Sensitivity for Pb(II): 0.0025
μA (μg/L)1
[162]
Standard solutions
of Cd(II) and Pb(II)
Whatman grade 1
chromatography
paper
Boron-doped
diamond paste
electrodes
(BDDPEs)
Square-wave
anodic stripping
voltammetry
(SWASV)
Print wax patterns
on microfluidic
paper;
stencil printed of
an electrode with a
Cd(II) and
Pb(II)
LOD for Cd(II): 25 g/L
LR for Cd(II): 25200 g/L
LOD for Pb(II): 1 g/L
LR for Pb(II): 1200 g/L
Sensitivity of Cd(II): 0.218
[100]
Sustainability 2022, 14, 12844 20 of 41
mixture of BDD
powder and
mineral oil
μA μM-1
Sensitivity of Pb(II): 0.305 μA
μM-1
Environmental and
biological samples
Cyclic olefin copol-
ymer (COC)
Bismuth
Square-wave
anodic stripping
voltammetry
(SWASV)
Photolithography
of COC
screen-printed
electrode (SPE)
Pb(II)
Cd(II)
LOD for Pb(II): 8 ppb; LOD
for Cd(II): 9.3 ppb
LR for Cd(II): 28−280 ppb
LR for Pb( II): 25−400 ppb
Sensitivity for Cd(II): 0.065
μA (μg/L)1
Sensitivity for Pb(II): 0.0022
μA (μg/L)1
[72]
Deionized (DI)
water for experi-
ments;
sample solution
(with HNO3 and
KCl ) for electro-
lyte;
silver electroplating
solution for Ag
electroplating
Cyclic olefin copol-
ymer (COC)
Silver
Square-wave
anodic stripping
voltammetry
(SWASV)
Spin-coated S1818-
positive photore-
sistor
patterned on a
COC substrate by a
photolithographic
technique;
microfabricated
silver electrodes
Pb(II)
LOD: 0.55 ppb
LR: 1−1000 ppb
Sensitivity: 0.028 μA (μg/L)1
[73]
Sample solution
containing lead
ions
Polymethylmethac-
rylate (PMMA)
Boron-doped
diamond elec-
trode
Square-wave
anodic stripping
voltammetry
(SWASV)
Microelectrodi-
alyser
combined with
boron-doped
diamond electrode
Pb(II)
LOD: 4 g/L
LR: 20100 g/L
Sensitivity of 15.5 nA L /g
[160]
Different electroac-
tive pollutants
Polymethylmethac-
rylate (PMMA)
Gold thin film
Anodic stripping
chronoamperome-
try (AS-CA)
Microfabrication
techniques (mi-
cromilling in
PMMA of micro-
fluidic channels;
photolithography
of gold thin-film
electrodes)
Cu(II)
LOD: <0.3 µM
[161]
Water solution
containing heavy
metal ions
Photosensitive resin
Screen-printed
electrode (SPE)
modified
with Mn2O3
Differential-pulse
anodic stripping
voltammetry
(DPASV)
Stereolithography
appearance (SLA)
for 3D-printed
microfluidic device
(prototyping);
microporous
screen-printed
electrode modified
with Mn2O3
Cd(II)
and Pb(II)
LOD for Cd(II): 0.5 g/L
LR for Cd(II): 0.5 to 8 g/L
LOD for Pb(II): 0.2 g/L
LR for Pb(II):10 to 100 g/L
[144]
Mixture of heavy
metal ions
PDMS/glass
Gold
Capillary electro-
phoresis with
contactless detec-
tion (CCD)
Spin-coated PDMS
membrane on a
glass substrate;
patterned elec-
trodes in an anti-
parallel configura-
tion
Heavy metal
ions
LOD: 0.4 M
[149]
Sample solution
containing mercury
ions
PDMS/glass
Screen-printed
electrode cou-
pled with
sodium-
dodecyl-
sulfate-doped
polyaniline
(PANiSDS
Cyclic voltamme-
try (CV) tech-
niques and
square-wave
voltammetry
(SWV)
Replica-molding
process for PDMS
channel; screen-
printed electrode
(SPE)
Hg(II)
LOD: 2.4 nM
LR: 6 nM to 35 nM
[163]
Seawater
PDMS/
glass
Platinum
Linear sweep
voltammetry
(LSV)
Soft lithography of
PDMS; patterning
of electrodes on
glass slides; plati-
num electrodeposi-
tion
Pb(II)
Cd(II)
LOD for Pb(II): 150 ppb
LOD for Cd(II): 340 ppb
[145]
Sustainability 2022, 14, 12844 21 of 41
Aqueous analyte
Paper substrate
Modifier-free
electrodes;
graphite foil
Square-wave
voltammetry
(SWV)
Cutting, stacking
Cd(II) and
Pb(II)
LOD for Cd(II): 1.2μg/L
LR for Cd(II): 5-500μg/L
LOD for Pb(II): 1.8 μg/L
LR for Pb(II): 5-100 μg/L
Sensitivity for Cd(II) and
Pb(II): 0.101 μA (μg/L)1
[157]
Lake water and
human serum
samples
3D paper-based
Gold nanopar-
ticles (NPs)
aggregates and
C nanocrystals
capped silica
NPs conjugated
with DNA
strands
Electrochemilu-
minescence (ECL)
Wax-
printing and
screen-printing
Pb(II) and
Hg(II)
LOD for Pb(II): 10 pM
LOD for Hg(II): 0.2 nM
LR for Pb(II): 30 nM - 1 M
LR for Hg(II): 0.5 nM - 1 M
[164]
4.4.2. Microfluidic Detection Systems for Phenols or Phenolic compounds
Environmental water from natural sources (e.g., seawater, water from lakes, rivers,
groundwater, etc.) can be contaminated with various pollutants (see Figure 1), including
phenols or phenolic compounds. Detection of toxic substances in water bodies is an
important issue in environmental monitoring.
Phenolic compounds are toxic substances and are among the 129 most polluting
and most harmful pollutants to human health and the environment controlled and
identified by the US Environmental Protection Agency [165].
Phenols and phenolic waste can originate from wastewater discharged by dyes,
pesticides, and enterprisesespecially petrochemical enterprises [166]or can be
generated during the production of synthetic polymers, such as phenolic resins resulting
from the use of coking coal in oil refineries. Another source of phenolic waste is
pesticides with phenolic skeletons; these pesticides, through degradation, release
phenolic compounds, which contaminate the environment. For instance, chlorophenols
are commonly used as pesticides, herbicides, and disinfectants in modern societies, and
can also be produced through chlorination of phenols during water disinfection
processes [167], etc.
The most common phenolic compounds are phenol, bisphenol A, catechol, cresol,
dopamine, epinephrine, 2,4-dichlorophenol, chlorophenols, etc. These phenolic
compounds are bioaccumulative in nature (air, water, food, animals, and plants), and
due to their persistence in nature and their high toxicity it is imperative that they and
their derivatives be detected quickly via in situ monitoring.
Compact systems suitable for on-site measurements of phenols are preferred, since
they offer the option of rapid warning and avoid the errors and delays inherent in
laboratory-based analyses [168]. The optical microfluidic detection methods presented in
Table 5 can detect phenolic compounds such as phenol, bisphenol A (BPA), dopamine,
[102], and catechol by fluorescence (LR: 9.79·10−6 to 7.50·10−4M) [169] or colorimetric
detection (LOD: 2 M, LR: 5-70 M [170]. Table 6 shows a summary of electrochemical
microfluidic detection methods for phenols or phenolic compounds, device substrate
and fabrication methods used for microchips and electrodes.
Sustainability 2022, 14, 12844 22 of 41
Table 5. Optical microfluidic detection methods for phenols or phenolic compounds.
Samples
Device Substrate (or
Components)
Detection Method
(and/or Mecha-
nism)
Fabrication Meth-
od
Analyte (Target)
Limit of Detection
(LOD)
Linear Range (LR)
Ref.
Tap water and river
water samples
Fisher brand filter paper
(P5; 09−801C) with a
diameter of 11 cm and a
medium porosity
Colorimetry
Inkjet printing and
a layer-by-layer
(LbL) assembly
approach (formed
by alternatively
depositing layers
of chitosan and
alginate polyelec-
trolytes) onto filter
paper
Phenolic com-
pounds (phenol,
bisphenol A
(BPA), dopa-
mine)
LOD: 0.86 (0.1)
μg/L
[102]
Environmental sam-
ples
Polyacrylamide film
Florescence (mo-
lecular absorption)
---
Catechol
LR: 9.79·× 106 to
7.50·× 104M
[169]
-Standard solutions
(mixtures) of cate-
cholamines;
-Human urine and
plasma samples
Fused silica fiber coated
with a polysty-
rene/divinylbenzene
resin (PS/DVB) film
Optical fiber bio-
sensor + chroma-
tographic separa-
tion
Mechanically un-
cladded; enzymatic
cladding; dip-
coating of single
optical fibers (OFs)
Dopamine,
norepinephrine,
epinephrine
LOD for dopa-
mine: 2.1 pg/mL;
LOD for norepi-
nephrine: 2.6
pg/mL; LOD for
epinephrine: 3.4
pg/mL
[171]
Homogeneous stock
solgel solution
Hybrid Nafion/solgel
silicate
glass
Optical biosensors
(crosslinking im-
mobilization
method of laccase
and 3-methyl2-
benzothiazolinone
hydrazone
(MBTH)
MBTH mixture
was deposited
onto a glass slide
and coated
Catechol
LOD: 0.33 mM
LR: 0.58.0 mM
[172]
Catechol in water
sample
Fe3O4@Au coreshell
nanoparticles
Colorimetric detec-
tion (absorbance
principle)
Laccase-Au-Fe3O4
nanoparticles
(NPs)
Catechol
LOD: 2 M
LR: 570 M
[170]
Since most phenols are oxidizable at moderate potentials, amperometry can serve
as a highly sensitive tool for their detection [168]. The amperometric tyrosinase (Tyr)-
based biosensors constitute promising technology for in situ phenol monitoring in
discrete or batch systems because of a number of advantages (i.e., high selectivity, easy
automation, fast response, potential for miniaturization, simple instrumentation, and
low production cost) compared to classic procedures, including instrumental methods.
Mayorga-Martinez et al. developed an amperometric CaCO3-PEI/Tyr-based
biosensor integrated in a flow microsystem, which is presented schematically in Figure
8b. The electrochemical microfluidic-integrated biosensor was composed of PDMS/glass,
with a graphite WE. The microchannel was fabricated in PDMS by soft lithography, and
screen-printed electrodes (SPEs) modified with CO3-polyethyleneimine were used.
The CaCO3-PEI/Tyr biosensor for phenol detection was evaluated by
chronoamperometry. The biosensors showed a rapid and sensitive bioelectrocatalytic
response, reaching about 95% of the steady-state current within 40s after each phenol-
addition step. The obtained biosensing performance was LOD: 10 nM; LR: 0.5 to 5 M
[173]. The same microdevice (Figure 8c) was used for the detection of phenols via
electrochemical impedance spectroscopy (EIS) [148]. They obtained good analytical
performance in phenol detection in terms of reproducibility, selectivity, sensitivity, and
limit of detection (LR: 0.01–10 μM and LOD: 4.64 nM).
Sustainability 2022, 14, 12844 23 of 41
Figure 8. The construction of a fluidic microsystem for phenol sensing: (a) schematic representa-
tion of the PDMS/glass microchip device components; (b,c) schematic diagrams of the integrated
dual microfluidic system for phenol removal and sensing (PEI—poly(ethyleneimine); Tyr
tyrosinase).
Table 6. Electrochemical microfluidic detection methods for phenols or phenolic compounds.
Samples
Device Substrate
(or Components)
Working
Electrode
Type
Detection
Method
Fabrication
Method
Analyte
(Target)
Limit of Detection (LOD)
Linear Range (LR)
Ref.
Domestic water
supplies;
sample solution:
2,4-
dichlorophenol
(2,4-DCP) mixed
with Folin
Ciocâlteu (FC)
reagent
Plastic microfluid-
ic chip with
incorporated
electrodes
Platinum
Potential dif-
ference
measurements
Sputtering
method of
deposition of
electrodes on
plastic film
2,4-
Dichloro-
phenol
LOD: 0.1 ppm
[167]
Contaminated
water sample with
phenols
Hybrid
PDMS/glass mi-
crochip
Graphite
Chronoam-
perometry.
Soft lithogra-
phy in PDMS
of microchan-
nel; SPE modi-
fied with
aCO3-poly
(ethylene-
imine) (PEI)
microparticles
(MPs) and
tyrosinase
(Tyr)
Phenols
LOD: 10 nM
LR: 0.5 to 5 M
[173]
Contaminated
water sample with
phenols
Hybrid polydime-
thylsiloxane
(PDMS)/glass
chrono-
impedimetric
microchip;
polyester sub-
strate for screen-
Graphite
Electrochemi-
cal impedance
spectroscopy
(EIS);
chrono-
impedimetric
detection of
phenols
Soft lithogra-
phy in PDMS
of channels;
sequential
deposition of
graphite ink
and Ag/AgCl
ink onto a glass
Phenols
LOD: 4.64 nM
LR: 0.01–10 μM
[148]
Sustainability 2022, 14, 12844 24 of 41
printed electrode
(SPE)
substrate for a
screen-printed
electrode (SPE)
Water samples
Polyethylene -
based films
Carbon
(screen-
printed
carbon
electrodes)
Micellar elec-
trokinetic
chromatog-
raphy with
electrochemical
detection
(MEKC-EC);
amperometric
detector
Screen-printed
carbon elec-
trodes (SPCEs)
Trace phe-
nolic com-
pounds
LOD: 100 × 1012150 ×
1012 M
[174]
Sample
waste;
mixture of dopa-
mine,
epinephrine, cate-
chol, and 4-
aminophenol
Poly(dimethylsilo
xane) (PDMS)
silicon
wafer
Cylindrical
carbon
electrodes
Cyclic volt-
ammetry (CV)
Silicon wafer
spin-coated
with SU-8
2035-negative
photoresistor;
micromolding
casting process
of liquid PDMS
prepolymer
Dopamine,
epineph-
rine, cate-
chol,
4-
aminophe-
nol
LOD for dopamine: 140
nM; LR for dopamine:
.14045.00 m
LOD for epinephrine: 105
nM;
LR for epinephrine: 0.105
47.90 m
LOD for catechol: 693nM;
LR for catechol: 0.693
188.10 m
LOD for 4-amino
phenol: 459 nM
LR for 4-aminophenol:
0.459159.10 m
[175]
Human blood and
urine samples
Fiber optics;
Teflon plug
Glassy
carbon
Chromatog-
raphy
electrochemical
detector
(HPLC-ED)
---
Epineph-
rine,
dopamine,
norepineph-
rine
LOD for epinephrine:
3.5 pg/mL
LOD for dopamine: 2.9
pg/mL
LOD for norepinephrine:
3.3 pg/mL
LR: 5125 pg/mL
[176]
4.4.3. Microfluidic Detection Systems for Nitrites, Nitrates, and Ammonia
Environmental monitoring of nitrogen speciesmainly nitrites and nitratesis
commonly performed using standard analytical techniques such as spectrophotometry,
ion chromatography [146], laser-induced fluorescence (LIF), electrochemical detection
(ED), and mass spectrometry (MS). For example, Fuji et al. [140] used a PDMS-based
optical microfluidic chip for the simultaneous determination of sulfites and nitrites in
aqueous samples (river-, pond-, and rainwater) by laser-induced fluorescence (LIF).
The schematic representation of the experimental setup of the integrated analytical
system for the simultaneous fluorescence determination of sulfites and nitrites is
presented in Figure 9a. Another innovative method was presented by Lopez-Ruiz et al.
[177], who developed a low-cost paper-based microfluidic device with a smartphone
application for the measurement of nitrite concentrations based on image analysis. The
application studied the change in the hue (H) and saturation (S) coordinates of the HSV
color space for different sensing areas by using a customized algorithm for the
processing of an image taken with the built-in camera. The results (LOD 0.52 mg/L)
show good use of a mobile phone as an analytical instrument [177]. In Table 7, a few
optical microfluidic detection methods for nitrites and nitrates are presented, along with
certain characteristics of the device used, fabrication methods, and the performance of
each microfluidic device.
Table 7. Optical microfluidic detection methods for nitrites and nitrates.
Sustainability 2022, 14, 12844 25 of 41
Samples
Device Sub-
strate
(or Compo-
nents)
Detection Method
(and/or Mecha-
nism)
Fabrication Meth-
od
Analyte (Tar-
get)
Limit of Detection
(LOD)
Linear Range (LR)
Ref.
Aqueous samples
(river-, pond-, and
rainwater)
PDMS/glass
microchip
Laser-induced
fluorescence (LIF)
Microchannels
made by photoli-
thography and
wet-etching meth-
ods;
microfabricated
glass template
Nitrites
LOD: 0.4 × 106 M
[140]
Drinking water con-
taining nitrites
PMMA
microfluidic
chip
Colorimetric
chemical analysis
(Griess method for
nitrite detection on
a chip)
Microchip fabrica-
tion: micromilling
and solventvapor
bonding procedure
Nitrites
LOD: 14x 10-6 M
[178]
Synthetic and natu-
ral water samples;
environmental and
drinking water
Whatman filter
paper grade 1
and 4
Colorimetry
Inkjet printing
method of elec-
trode;
patterning grade 1
and 4 filter paper
(Whatman)
Nitrites
and nitrates
LOD for nitrites: 1 m
LOD for nitrates: 19
m
[179]
Water samples
Standard labor-
atory Whatman
paper grade 1
Colorimetry
Stamping tech-
nique of the paper-
based
microfluidic devic-
es
nitrites
LOD: 0.52 mg/L
[177]
Figure 9. The construction of a fluidic microsystem for nitrites and sulfites: (a) schematic represen-
tation of the experimental setup of the integrated analytical system for the simultaneous fluores-
cence determination of sulfites and nitrites (b) schematic representation of a low-cost paper-based
microfluidic device and smartphone application for the measurement of nitrite concentrations
based on image analysis.
For real-time electrochemical detection, Gallardo-Gonzalez et al. [180] used a
microfluidic device that consisted of PDMS (obtained by soft lithography) and a fully
integrated chemical sensing platform (with four working microelectrodes, two Ag/AgCl
reference microelectrodes, one Pt auxiliary electrode, and one counter microelectrode).
The construction of the abovementioned fluidic microsystem for the detection of
ammonium is presented in Figure 10a,b.
Sustainability 2022, 14, 12844 26 of 41
Figure 10. The construction of fluidic microsystems for the detection for ammonium and nitrate:
(a) The components of transducers and negative-shaped silicon molds bearing the microfluidic el‐
ements. (b) The illustration of the electrochemical sensor chip.
The real-time potentiometric measurements in flowing water showed that the
microfluidic device was still functional and responded to samples containing
ammonium after being immersed in the sewage for at least 15 min. Therefore, the low-
cost, low-power, easy-to-operate, miniaturized device developed by Gallardo-
Gonzalez's team can be used for in situ and real-time potentiometric measurements in
running water [180].
Aravamudhan et al. [181] developed a microfluidic nitrate-selective sensor based on
polypyrrole-doped nanowires. Cyclic voltammetry, amperometry, and flow-through
analysis were performed to evaluate the sensor’s performance for the determination of
nitrate ions in two sets of calibration solutions (DI water and IAPSO standard seawater).
By using the electrochemical doping approach on polypyrrole nanowires, a highly
sensitive (1.17-1.65 nA/M) and selective nitrate sensor was demonstrated on an MEMS
microfluidic platform. The sensor showed a linear response to nitrate of 10 M (0.14
nitrate-N) to 1 mM (14 ppm nitrate-N) [181]. Table 8 shows synthetized electrochemical
microfluidic detection methods for nitrites, nitrates, and ammonia.
Table 8. Electrochemical microfluidic detection methods for nitrites, nitrates, and ammonia.
Samples
Device Substrate
(or Components)
Working
Electrode
Type
Detection
Method
Fabrication Method
Analyte
(Target)
Limit of Detection
(LOD)
Linear Range (LR)
Ref.
Wastewater;
ammonium-
containing sam-
ples
PDMS microfluidic
device;
silicon substrate
wafers
Gold
Cyclic voltam-
metry (CV)
Microelectrodes
made by physical
vapor deposition
(PVD) followed by
photolithography
and lift-off;
soft lithography and
replica molding of
PDMS microfluidic
systems
Ammoni-
um
LOD: 4 × 10-5 M
[180]
Real-world sam-
ples;
nitrate samples
Silicon sub-
strate/polyimide
protective layer
Silver thin
film
Double-
potential-step
Chronocoulom-
etry (DPSC)
Patterned polyimide
insulation layer
NO3 -
LOD: 475 M
LR: 5002000 M
[182]
Seawater
Polypyrrole-
covered carbon
Polypyrrole
(PPy)-doped
Double-
potential-step
Patterned electro-
chemical reagent
NO3 -
LOD: 4.5 M
sensitivity: 1.17
[181]
Sustainability 2022, 14, 12844 27 of 41
nanowire
nanowires
(NWs ) on
the interdigi-
tated Pt
chronocoulome-
try (DPSC)
chamber of the sen-
sor chip using a thick
SU-8 film;
assembly of PPy
NWs on the Pt lines
using dielectropho-
resis
1.65 nA/M
Wastewater,
tap water;
river sample
Borosilicate glass
tube
Carbon disk
electrode
modified
with meso-
porous car-
bon material
(CMK-3)
Capillary elec-
trophoresis with
amperometric
detection and
electrochemical
impedance
spectroscopy
Carbon disk elec-
trode constructed
using a pencil lead
1,3,5-
Trinitro-
benzene
(TNB),
1,3-
dinitroben
zene
(DNB),
2,4,6-
trinitrotol
uene
(TNT),
2,4-
dinitrotolu
ene (DNT)
LOD for TNB: 4
g/L
LOD for DNB: 4.1
g/L
LOD for TNT: 4.7
g/L
LOD for DNT: 3
g/L
LR for TNB: 10.7
4.7 × 10 3 g/L
LR for DNB: 8.43.7
× 10 3 g/L
LR for TNT: 11.4
5.0 × 10 3 g/L
LR for DNT: 9.14.0
× 10 3 g/L
[183]
Dirty aquarium
water samples (in
the absence and
presence of fish-
es) and Meia
Ponte River wa-
ter samples
Commercial glass
substrate for device
(borosilicate glass
microchips with
integrated elec-
trodes)
Integrated
electrodes
Capacitively
coupled contact-
less conductivity
detection (C4D)
------
NO3
NO2-
LOD for NO3: 4.4
M
LOD for NO2: 4.9
M
[146]
River water, tap
water, mineral
water
PMMA microchip,
Isotachophoresis
(ITP) and column-
coupled capillary-
zone electrophore-
sis (CZE)
Thin-film
platinum
electrodes
Conductivity
Microchip fabrica-
tion: substrate hot
embossing; metalli-
zation of the PMMA
covers used as the
cover plates; sputter-
ing deposition of
thin-film platinum
electrodes
Nitrites
LOD: 0.50.7 M
[184]
4.4.4. Microfluidic Detection Systems for Pathogens
Pathogens are infectious microorganisms such as bacteria, viruses, protozoans,
fungi, or other microorganisms that can cause diseases in humans, animals, and plants.
The most common pathogens with absorbance techniques are Escherichia coli,
Saccharomyces cerevisiae, and Aeromonas hydrophila [136,185]. Many researchers have
studied cholera toxins, Bacillus globigii [186], Staphylococcal enterotoxin B [187], Listeria
monocytogenes, Salmonella [188], and E. coli [189] using fluorescent techniques. The
parameters/performance of the optical microfluidic systems/biosensors, along with the
components and fabrication methods of the devices, are presented in Table 9.
Sustainability 2022, 14, 12844 28 of 41
Table 9. Optical microfluidic detection methods for pathogens.
Samples
Device Substrate
(or Components)
Detection
Method
Fabrication Meth-
od
Analyte (Tar-
get)
Limit of Detection (LOD)
Linear Range (LR)
Ref.
Samples of micro-
organism-infected
water
Glass substrate;
dry-film resist
(DFR)-based
microfluidic chip
bonded with mul-
timode fiber pigtails
Absorbance
measurements
(optical)
Photolithographic
fabrication of mi-
crochannels
Escherichia coli,
Saccharomyces
cerevisiae, and
Aeromonas
hydrophila
LOD for A. hydrophila
and E. Coli: 1.0 × 105
cells/mL
LOD for S. cerevisiae: 1.0 ×
106 cells/mL
[185]
Strains of
Aeromonas hy-
drophila
Glass substrate
Absorbance
measurements
(optical)
Photolithographic
fabrication of mi-
crochannels
Aeromonas
hydrophila
LOD: 6 L or 102 cells/mL
[136]
Infected water
samples
Soda lime glass
substrate of micro-
fluidic chip (NS-
12A, PerkinElmer,
USA)
Fluorescence
detection
-
E. coli
LOD: 10 4 CFU/mL
[189]
Real samples; bio-
logical samples;
spiked drinking
water
Glass fiber;
nitrocellulose
membrane; inte-
grated paper-based
biosensor; hydro-
phobic PVC layers;
separation of paper
Lateral flow
assays
(LFA) for bacte-
rial nucleic acid
detection;
colorimetry
Cell deposition
E. coli
LOD: 10 CFU/mL (Water)
[190]
Samples containing
mixtures of analytes
PDMS/glass
Fluorescence
-
Cholera toxin;
Staphylococcal
enterotoxin B;
Bacillus globigii
LOD for cholera toxin: 8
ng/mL;
LOD for Staphylococcal
enterotoxin B: 4 ng/mL;
LOD for Bacillus globigii:
6.2×104 cfu/mL
[186]
Phosphate-buffered
saline samples
Polyethylene chan-
nel
Fluorescence
-
Staphylococcal
enterotoxin B
LOD: 5 ng/mL
[187]
Chicken carcass
wash samples
Glass/hybrid
Fluorescence
-
E. coli
LOD: 20 organism
[191]
Real samples
3D PDMS sponge
Fluorescence
The powdered salt
particles were
rubbed by adding
water and then cast
into molds (empty
syringe) to shape
the template for a
PDMS sponge
Listeria mono-
cytogenes, Sal-
monella sp.
Salmonella
typhimurium
LOD for: 10 3 to 10 4
CFU/mL
LOD for: 1.5 x 10 2 CFU/
mL
[188]
Compared with the traditional approaches, various electrochemical biosensors have
been also constructed and used to detect pathogens, due to their advantages of
simplicity, low cost, sensitivity, and easy miniaturization [192,193]. The principle of
electrochemical biosensors for pathogens is mainly based on the specific recognition
between various identification elements and targets, which can lead to changes in the
detectable signal. For instance, Liu and coworkers [194] fabricated a facile, label-free,
cheap electrochemical Salmonella biosensor with satisfactory performance. The sensor
also showed its specificity among different Salmonella serotypes, selectivity for different
types of bacterial cells, and ability to distinguish between dead and live cells with a total
Sustainability 2022, 14, 12844 29 of 41
detection time of 1 hour. The characteristics and construction of these biosensors can be
found in Figure 11a,b.
Moreover, a microfluidic device for label-free detection of Escherichia coli in
drinking water was developed by Myounggon et al. [195]. This type of microfluidic
sensor, as shown in Figure 11a,b, can accurately quantify microorganisms that are
present in low numbers (100 CFU/mL) in a high-throughput manner.
Figure 11. The construction of electrochemical microfluidic systems for the detection of pathogens:
(a) a microfluidic sensor with a region that employs dielectrophoretic impedance measurements
for the detection of E. Coli microorganism; (b)the schematic representation of a microfluidic bio-
sensor for Salmonella.
In Table 10, the electrochemical microfluidic detection methods for E. coli, S. aureus,
Salmonella serogroups, etc., along with the characteristics of the microfluidic devices and
their performance, are summarized.
Table 10. Electrochemical microfluidic detection methods for pathogens.
Samples
Device Substrate
(or Components)
Working
Electrode
Type
Detection
Method
(and/or Mech-
anism)
Fabrication Method
Analyte
(Target)
Limit of Detec-
tion (LOD)
Linear Range (LR)
Ref.
Bacteria-
contaminated
drinking water
samples;
mixture of bacte-
rial suspensions
PDMS microfluid-
ic chip
Gold
Dielectropho-
retic imped-
ance measure-
ments
Conventional photo-
lithographic and soft
lithographic tech-
niques for a PDMS
microfluidic chip;
PVD (sputtering) for
the electrode materi-
al
E. coli
LOD:
300 CFU/mL
[195]
Mixed bacterial
sample of E. coli
O157:H7 and S.
aureus
Polyethylene
glycol (PEG)-
based microfluidic
chip integrated
with a functional-
ized nanoporous
alumina mem-
brane
Platinum
Linear sweep
voltammetry
(LSV)
Soft lithography
techniques
E. coli and
S. aureus
LOD:
100 CFU/mL
[196]
Real sample
Poly (dimethyl
siloxane) (PDMS)
substrate
Carbon
Linear sweep
voltammetry
(LSV)
Soft lithography
techniques for micro-
channels
E. coli (DNA)
LOD:
24 CFU/mL
[197]
E. coli samples
Poly(methyl
methacrylate)
Gold
Cyclic voltam-
metry and
-
E. coli
LOD: 1.99 ×
1043.98 × 109
[198]
Sustainability 2022, 14, 12844 30 of 41
(PMMA)/silicon
dioxide wafer
amperometric
measurements
CFU/mL
Salmonella sam-
ples
PDMS/glass
Interdigitat-
ed electrode
(IDE)
Impedance
Surface microm-
achining technology
for sputtering of Cr
and Au on top of
glass (SU8 type);
PDMS bonding to
seal the microchannel
Salmonella
serogroups
LOD:
7 cells/mL
[199]
Bacterial samples
Glass substrate
Interdigitat-
ed array and
gold microe-
lectrode
Impedance
3D printing and
PDMS casting of
microchannels
Escherichia
coli O157:H7
LOD:
12 CFU/mL
[200]
Salmonella-
specific aptamer
probes
SU-8 substrate
and
suspended carbon
nanowire
Carbon
nanowire
electrodes
Electrical detec-
tion/chemiresis
tive
Nanowires were
deposited by electro-
spinning; photoli-
thography for SU-8
support structure.
Salmonella
typhimurium
LOD:
10 CFU/mL
[201]
Real samples of S.
typhimurium cells
PDMS/glass for
substrate;
graphene oxide
(GO)
nanosheets
wrapped in car-
boxylated multi-
walled carbon
nanotubes
(cMWCNTs)
composite
GO-
cMWCNTs
microelec-
trode
Electrochemical
detection
Soft lithography for
PDMS microchan-
nels;
wet
chemical etching
process for fabrica-
tion of microelec-
trodes
Salmonella
typhimurium
bacterial cells
LOD:
0.376 CFU/mL
[202]
Listeria cells,
magnetic nano-
particles (MNPs)
modified with
anti-Listeria mon-
oclonal antibod-
ies, and gold na-
noparticles
(AuNPs) modified
with anti-Listeria
polyclonal anti-
bodies and urease
PDMS/glass
Interdigitat-
ed microe-
lectrode
Impedance
3D printing and
surface plasma bond-
ing
Listeria
monocyto-
genes
LOD:
10 6 CFU/mL
[203]
The information presented in this chapter is summarized in Figure 12. In this figure,
(i) the different sample types used in pollution analysis and monitoring of the
contaminants, (ii) the device substrate types, and (iii) the materials of the working
electrode used as sensing units for electrochemical sensors integrated into the
microfluidic devices are shown schematically, along with (iv) the detection methods for
both types of microfluidic sensors.
Sustainability 2022, 14, 12844 31 of 41
Figure 12. The schematic diagram of the two types of microfluidic sensors for pollution analysis,
with sensing and detection units.
5. Conclusions and Future Perspectives
In line with the Goal 3 of the 2030 Agenda for Sustainable Development
“Transforming our world: the 2030 Agenda for Sustainable Development”—"Ensure
healthy lives and promote well-being for all at all ages"and also consistent with the
statement that "human well-being is closely linked to environmental health", it is
necessary and beneficial for sustainable development that people have access to clean air
to breathe, fresh water to drink, and places to live free of toxic substances and hazards.
In this context, to support these vital needs, our overview of previous and recent
research in the design and fabrication of optical and electrochemical microfluidic devices
and microfluidics-integrated (bio)sensors for pollution analysis, in correlation with their
environmental applications, offers a wide-ranging contribution to a synthetic picture of
the most-used and best-performing microfluidic devices and their roles in field-
monitoring measurements at lower cost and reduced pollutant reagent consumption.
In addition, the advantages and disadvantages of the various materials and
techniques used for component fabrication, along with the benefits of miniaturization
and integration of optical and electrochemical (bio)sensors in pollution analysis, were
highlighted. Challenges in biosensors point to the need for the development of
innovative portable analytical instruments that integrate optical or electrochemical
sensors on microfluidic platforms. In the field of biosensors, further research and
innovation should enable the manufacturing of sensitive and inexpensive portable
microfluidic biosensors capable of monitoring soil contaminants, prompting timely
action to prevent the spread of pollutants and contaminating agents in the environment.
The availability of such integrated microfluidic biosensors could significantly reduce
environmental pollution and enable continuous and real-time monitoring of
environmental contaminants.
Future challenges consist of finding innovative ways to improve the reproducibility
and reliability of microfluidic devices integrated into sensors, to increase their accuracy
in detecting multiple contaminants simultaneously in the field. In the future, it is
Sustainability 2022, 14, 12844 32 of 41
expected that the applicability of sensors integrated into microfluidic systems and other
types of microfluidic devicesfor example, in the analysis of microplastic [204] or
nanoplastic materials in rivers, lakes, or oceanswill be expanded.
Author Contributions: Conceptualization, B.A. and I.N.P.; methodology, B.A., I.N.P. and R.V.;
validation, R.V. and I.N.P.; investigation, I.N.P.; writingoriginal draft preparation, I.N.P. and
R.V.; writingreview and editing, B.A., I.N.P., R.V. and C.O.R. visualization, C.O.R.; supervision,
R.V. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Informed Consent Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
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