sensors

Review
MXenes-Based Bioanalytical Sensors: Design,
Characterization, and Applications
Reem Khan and Silvana Andreescu *
Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York, NY 13676, USA;
[email protected]
* Correspondence: [email protected]




Received: 23 August 2020; Accepted: 18 September 2020; Published: 22 September 2020


Abstract: MXenes are recently developed 2D layered nanomaterials that provide unique capabilities for
bioanalytical applications. These include high metallic conductivity, large surface area, hydrophilicity,
high ion transport properties, low diffusion barrier, biocompatibility, and ease of surface functionalization.
MXenes are composed of transition metal carbides, nitrides, or carbonitrides and have a general
formula Mn+1 Xn , where M is an early transition metal while X is carbon and/or nitrogen. Due to their
unique features, MXenes have attracted significant attention in fields such as clean energy production,
electronics, fuel cells, supercapacitors, and catalysis. Their composition and layered structure make
MXenes attractive for biosensing applications. The high conductivity allows these materials to be
used in the design of electrochemical biosensors and the multilayered configuration makes them
an efficient immobilization matrix for the retention of activity of the immobilized biomolecules.
These properties are applicable to many biosensing systems and applications. This review describes
the progress made on the use and application of MXenes in the development of electrochemical
and optical biosensors and highlights future needs and opportunities in this field. In particular,
opportunities for developing wearable sensors and systems with integrated biomolecule recognition
are highlighted.

Keywords: MXenes; 2D nanomaterials; biosensors; wearables

1. Introduction
Since the discovery of graphene, two-dimensional (2D) nanomaterials have gained significant
attention due to their high surface area, electrical conductivity, functionalized surfaces,
and mechanical properties. Prime examples include materials such as silicene, germanene, boron nitride,
and molybdenum sulfide. 2D materials offer exceptional physical, chemical, and structural properties
that make them useful in a wide variety of applications such as sensors, energy storage and conversion,
optoelectronics, and catalysis. MXene is an emerging class of 2D transition metal carbide, nitride,
or carbonitride added to the 2D nanomaterial group initially developed by Gogotsi and coworkers in
2011 [1]. MXenes have general formula Mn+1 Xn where M is an early transition metal while X is carbon
and/or nitrogen, synthesized by the selective etching of MAX phases [2]. MAX phases are layered
ternary carbides and nitrides with a general formula Mn+1 AXn , where A represents elements from
the group 13 and 14 of the periodic table. The term MAX phases were established in the late 1990s,
but most of these phases were discovered 40 years ago. A renewed interest in the application of MAX
phases started in 1996 due to their unusual combination of chemical, physical, electric, and mechanical
properties resulting from their layered structure supported by a strong mixed metallic-covalent M X
bond and a relatively weak M A bond [3].
To date, 70 different MAX phases have been reported, while more than 20 members of the MXenes
family have been synthesized, and dozens more are predicted, making it one of the fastest-growing 2D

Sensors 2020, 20, 5434; doi:10.3390/s20185434 www.mdpi.com/journal/sensors

Sensors 2020, 20, 5434 2 of 19

material families. Typically, 2D materials MXene are synthesized by removing the A layer from their
parent MAX (remaining MX-) phases and are structurally similar with graphene (hence named -ene).
Additionally, the MXene family comes in three atomic structures, ranging from M2 X to M3 X2 and M4 X3 ,
yielding tunability, and opportunity to discover and mold materials based on application requirements.
Recently, the MXene family has been expanded to include double transition metal MXenes with
formula M0 2 M”C2 and M0 2 M”2 C3 .
The most successful synthesis route of Ti3 C2 involves the wet chemical etching in hydrofluoric
(HF) acid or HF containing/forming etchants. The wet chemical route is based on three simple
steps: (1) Etching, (2) delamination, and (3) intercalation. Due to the use of HF as an etchant,
MXene layers are primarily terminated with F and OH/=O functional groups, abbreviated as Tx to
give a general formula of Mn+1 Xn Tx , n = 1–3. The etching is simply done by immersing the MAX
phase in HF. Alhabeb et al. studied the effect of different concentrations of HF on the morphology
of the resulting MXene. The results of the study have shown that Al can be etched by using
HF concentration as low as five weight percent; however, for low HF concentrations, the MXene
did show the characteristic accordion-like morphology that was observed in the case of 30% HF.
After completing the etching process, the powder was washed thoroughly with deionized water by
successive centrifugation cycles at 3500 rpm. After each cycle, the supernatant was decanted and
replaced with fresh deionized water. The washing process continued until the pH of the supernatant
has reached 6 to 7. Delamination is the second crucial step in the synthesis protocol that enhances the
accessible surface area of the nanomaterial. In order to delaminate MXene nanosheets, the van der Waals
forces between the adjacent MX sheets have to be broken. This barrier is relatively strong for MXenes
(with their ~2.2 Å interlayer distance) compared to that of graphene (3.35 Å). A well-established method
for the delamination of MXenes is to increase the interlayer distance through intercalation, achieved by
inserting external elements (ions or molecules) in between the layers of the laminated material.
Large, organic molecules, such as dimethyl sulfoxide (DMSO), isopropylamine, tetraalkylammonium
hydroxides (TBAOH), were some of the first intercalants used for expanding the interlayer spacing of
Ti3 C2 Tx MXenes synthesized with HF [4]. Figure 1 shows a general synthesis scheme for producing
MXenes (left) and examples of SEM micrographs (right) displaying the ‘accordion’-like morphology
that is typical of various MXenes compositions. For description of detailed synthesis methodologies,
readers are referred to other literature, specifically discussing the synthesis protocol of MXenes [5,6].
Most applications of these materials to date are in energy conversion, catalysis, and electronics
with emerging areas in structural, biomedical, and environmental fields [7–9]. The biosensing and
analytical measurement field remains relatively unexplored and provides unique opportunities for
future development.
Several prior works summarized the application of MXenes in chemical sensors [10],
particularly gas sensors [11] and their environment-related applications [10–13]. Here we focus on the
properties and suitability of MXenes as an immobilization matrix, signal transducer, and amplifier of
biomolecular recognition for the design of biological sensors. The first half of the review provides an
overview of the physical and chemical properties of MXenes that are of interest for the development
of bioanalytical sensors. The second half discusses specific examples of MXenes-based biosensors
with enzyme, antibodies, DNA, and aptamer recognition, and highlights recent developments on the
use of MXenes as supporting material for wearable devices.
 (left) and examples of SEM micrographs (right) displaying the ‘accordion’-like morphology that is
typical of various MXenes compositions. For description of detailed synthesis methodologies, readers
are referred to other literature, specifically discussing the synthesis protocol of MXenes [5,6]. Most
applications of these materials to date are in energy conversion, catalysis, and electronics with
emerging areas in structural, biomedical, and environmental fields [7–9]. The biosensing and
Sensors 2020, 20,measurement
analytical 5434 3 of 19
field remains relatively unexplored and provides unique opportunities for
future development.

Figure 1. (Left) Schematic for the exfoliation process of MAX phases and formation of MXenes. (right)
Figure 1. (Left) Schematic for the exfoliation process of MAX phases and formation of MXenes.
SEM micrographs for (A) Ti3AlC2 MAX phases, (B) Ti3AlC2 after HF treatment, (C) Ti2AlC after HF
(right) SEM micrographs for (A) Ti3 AlC2 MAX phases, (B) Ti3 AlC2 after HF treatment, (C) Ti2 AlC after
treatment, (D) Ta4AlC3 after HF treatment, (E) TiNbAlC after HF treatment, and (F) Ti3AlCN after HF
HF treatment, (D) Ta4 AlC3 after HF treatment, (E) TiNbAlC after HF treatment, and (F) Ti3 AlCN after
treatment. Reprint with permission [2]. Copyright © 2012, American Chemical Society.
HF treatment. Reprint with permission [2]. Copyright © 2012, American Chemical Society.

2. Properties of MXenes for Bioanalytical Sensing

2D nanomaterials such as graphene, MoS2 , boron nitride nanosheets, either alone or in
nanocomposite form, have demonstrated superior properties such as high surface area platforms
for the construction of different types of chemical and biological sensors. When used in
sensing design, these materials improved the performance of sensors in terms of sensitivity, selectivity,
and analyte binding. However, limitations such as high hydrophobicity, low biocompatibility,
low electrical conductivity, and difficulty in surface functionalization limit their incorporation in sensor
design at a commercial scale. MXenes complement the emerging class of 2D materials and provide
advantages for sensors design in terms of hydrophilicity, electrical conductivity, biocompatibility,
and above all, ease of functionalization due to the presence of surface functional groups. Furthermore,
MXene has high intercalation capacity, which is missing in other 2D nanomaterials. A comparison of
the fundamental characteristics of different nanomaterials is given in Table 1.

Table 1. Comparison of fundamental properties of various nanomaterials.

Surface Area Conductivity Band Gap

Nanomaterials Biocompatibility References
(m2 g–1 ) (S/cm) (eV)
Graphene 450 2700 0 Biocompatible [14–16]
h-Boron Dependent on
150–550 insulator 5.9 [17,18]
nitride size and shape
Unclear /under
SWCNT 600 102 –106 0.042 [19–21]
debate
Unclear/under
MWCNT 122 103 –105 1.82 [19,20,22]
debate
MoS2 8.6 10−4 1.89 Biocompatible [23–25]
δ-MnO2 257.5 10−5 to 10−6 1.33 Biocompatible [15,26,27]
MXene
93.6 2410 0.1 Biocompatible [28–30]
(Ti3 C2 )

The high electrical conductivity, thermal stability, hydrophilic nature, large interlayer spacing,
high surface area, and easily tunable structure make this new family of 2D nanomaterials extremely
attractive for a wide variety of applications. Because MXenes have a relatively low number of
 Sensors 2020, 20, 5434 4 of 19

atomic layers, a single stack of MXene layers is typically less than 1 nm thickness, while the lateral
dimension is in the nm to µm range, depending on the composition, synthesis, and processing steps.
SensorsMoreover,
2020, 20, xbyFORselecting double metal MXenes, it is possible to tune the valence states and relativistic
PEER REVIEW 4 of 19
spin-orbit coupling [31]. Furthermore, the MXenes have a ceramic-like nature that is responsible for their
high chemical and mechanical stability. However, unlike traditional ceramics, MXenes have inherent
applications. The ease of functionalization is a particularly important feature of using MXenes in the
conductivity and a significantly larger surface area imparted by the composition and layered structure
design of bioanalytical sensors that require materials with abundant functional groups at their
of their molecular sheets made of carbides and nitrides of transition metals such as Ti. In addition,
surface. This high
the MXene surface
surface can befunctionality,
functionalized in withaddition
differentto their layered
functional groups structure,
that provides provides
numerous the ability to
bind,opportunities
protect, andforretain
surfacethe
stateactivity of biomolecules
engineering, greatly extending fortheir
specific targeting
properties and recognition
and applications. The ease properties
of functionalization is a particularly important feature of using MXenes in the
that are essential for bioanalytical sensing. The versatility and compositional variety make MXene an design of bioanalytical
sensors that diverse
extraordinarily require materials with abundant
and appealing class offunctional
materials groups at their surface.[31].
for applications This high surface
functionality, in addition to their layered structure, provides the ability to bind, protect, and retain
In the last 10 years, there has been growing interest in exploring the use of MXenes in the design
the activity of biomolecules for specific targeting and recognition properties that are essential for
of supercapacitors
bioanalytical sensing. [32,33], transparent
The versatility conductors variety
and compositional [34,35],make field-effect transistors [36], Li-ion
MXene an extraordinarily
batteries [37,38],
diverse electromagnetic
and appealing interface
class of materials shielders [39],
for applications [31]. catalysts [40], hybrid nanocomposites [41],
In the last 10composites
fillers in polymeric years, there has beendual-responsive
[42], growing interest in surfaces,
exploring the use of MXenes
purifiers, in the
[43,44] design substrates
suitable of for
supercapacitors [32,33], transparent conductors [34,35], field-effect transistors
dyes [45], photocatalysts for hydrogen production [31], methane storage [46], and as well as [36], Li-ion batteries [37,38],
electromagnetic interface shielders [39], catalysts [40], hybrid nanocomposites [41], fillers in
photothermal conversion [47]. Applications in electronic [48,49], magnetic [50,51], optical [1,52,53],
polymeric composites [42], dual-responsive surfaces, purifiers, [43,44] suitable substrates for
thermoelectric [54,55], and sensing
dyes [45], photocatalysts for hydrogen devices [5,56] are
production [31],being
methaneexplored
storagewhile newasutilizations
[46], and well as such as
reaction media toconversion
photothermal facilitate[47].
catalytic and photocatalytic
Applications in electronic [48,49], processes, hydrogen
magnetic [50,51], storage
optical [1,52,53],[57,58], and
thermoelectric
nanoscale [54,55], and sensing
superconductivity [59] aredevices [5,56] to
beginning arebe being explored while
investigated. Some newof utilizations
the MXenes such
are predicted
as reaction media to facilitate catalytic and photocatalytic processes, hydrogen
to be topological insulators with large band gaps involving only d orbitals [60,61]. This review focuses storage [57,58],
and nanoscale superconductivity [59] are beginning to be investigated. Some of the MXenes are
on the applications of MXenes in the field of biological sensors, where MXenes have been used as an
predicted to be topological insulators with large band gaps involving only d orbitals [60,61]. This review
electrode
focusesmaterial exploiting
on the applications of their
MXenes high catalytic,
in the high surface
field of biological sensors,area,
wherecharge
MXenestransport properties, and
have been used
biocompatibility
as an electrode with
material biological
exploiting matrices. The different
their high catalytic, high surfaceclasses of biosensing
area, charge platforms and the
transport properties,
and biocompatibility with biological matrices.
applications covered in this review are summarized in Figure 2. The different classes of biosensing platforms and the
applications covered in this review are summarized in Figure 2.

Figure 2. Summary of different classes of biosensing platforms based on MXenes and their applications.
Figure 2. Summary of different classes of biosensing platforms based on MXenes and their
Immunosensors (reprinted with permission from [62]) Aptasensors (reprinted with permission
applications.
from [63]), Immunosensors (reprinted
Enzyme sensors (reprinted with permission
with permission from [64]). from [62]) Aptasensors (reprinted with
permission from [63]), Enzyme sensors (reprinted with permission from [64]).

3. Classes of Bioanalytical Sensors Based on MXenes

3.1. Enzyme Sensors

Enzymes, as a bio-recognition element, offer distinct advantages such as substrate specificity
Sensors 2020, 20, 5434 5 of 19

3. Classes of Bioanalytical Sensors Based on MXenes

3.1. Enzyme Sensors

Enzymes, as a bio-recognition element, offer distinct advantages such as substrate specificity and
high efficiency under mild conditions. Enzyme based electrochemical biosensing devices have been
developed extensively in the last few decades [1]. Despite progress, enzymes can lose their bioactivity
when directly immobilized onto electrode surfaces. Moreover, due to the deeply rooted location
of redox-active centers in enzymes, the direct electron transfer (DET) between these biomolecules
and the electrode surface is generally difficult and has been the subject of extensive investigations
as reviewed in a recent work [65]. Therefore, the use of nanomaterials has been found beneficial to
facilitate the electron transfer along with promoting retention of the bioactivity of immobilized enzymes.
Among different types of nanomaterials, 2D nanomaterials proved to be effective for improving the
DET from the enzyme to the transducer surface. Because MXene have a high surface to volume ratio
and are biocompatible, they provide a highly suitable matrix for the fabrication of enzymatic biosensors.
They can be used as a supporting platform for the immobilization of enzymes, promote diffusion,
and accelerate the electrode kinetics, thus improving DET transfer. MXenes are also expected to enhance
sensitivity and lower the detection limit of sensing devices. The most explored application of MXenes
reported in the literature is for glucose sensing using glucose oxidase (GOx) immobilized within stacked
layers of MXenes. For example, Chia et al. reported a Ti3 C2 MXene, produced via HF etching and
subsequent delamination with tetrabutylammonium hydroxide (TBAOH), as a transducer platform
for the development of an electrochemical glucose biosensor with chronoamperometric detection.
The biosensor exhibited high selectivity and good electrocatalytic activity toward the detection
of glucose, with a linear range spanning from 50 to 750 µM and a limit of detection (LOD) of 23.0 µM
(Figure 3) [64].
Other works explored hybrid configurations that combine the layered structure of MXenes
with the properties of other materials to add additional functions. Gu et al. constructed a porous
MXene-graphene (MG) nanocomposite-based glucose biosensor [66]. The 3D porous nanostructure
was prepared using a mixing-drying process in which the size of the pores was controlled by tuning the
content of Ti3 C2 and graphene. The synthetic methodology and the preparation process of the sensor
are displayed in Figure 4. The porous structure provided more open structures to embed GOx within
the internal pores, favoring retention of the GOx activity. The biosensor exhibited good electrocatalytic
properties towards glucose biosensing for the detection of glucose in human sera.
Other improvements have been achieved by decorating the surface of MXenes with metal
oxide nanoparticles (NPs), further increasing the surface area and conductivity of the electrodes and
maximizing the enzyme loading. A composite of Nafion-Au NPs-MXene was reported as electrode
material for the immobilization of GOx and subsequent detection of glucose [67]. The synergistic
effects of Au NPs and MXene sheets resulted in unique electrocatalytic properties, which enabled
the detection of glucose in the µM to mM range. Similarly, Ti3 C2 Tx nanosheets were modified
with β-hydroxybutyrate dehydrogenase and then used as a biosensor for amperometric sensing of
β-hydroxybutyrate, a biomarker for diabetic ketoacidosis. The developed biosensor best operated at a
potential of −0.35 V (vs. Ag/AgCl), displayed a linear range between (0.36 to 17.9 mM), a sensitivity
of 0.480 µA mM−1 cm−2 , and a LOD of 45 µM. Later, the biosensor was successfully applied to the
determination of β-hydroxybutyrate in (spiked) real serum samples [68].
sensing using glucose oxidase (GOx) immobilized within stacked layers of MXenes. For example,
Chia et al. reported a Ti3C2 MXene, produced via HF etching and subsequent delamination with
tetrabutylammonium hydroxide (TBAOH), as a transducer platform for the development of an
electrochemical glucose biosensor with chronoamperometric detection. The biosensor exhibited high
Sensors 2020, and
selectivity 20, 5434 6 of 19
good electrocatalytic activity toward the detection of glucose, with a linear range
spanning from 50 to 750 µM and a limit of detection (LOD) of 23.0 µM (Figure 3) [64].

Figure
Figure3.3.(A)
(A)Schematic
Schematicillustration
illustrationofofsensor
sensorfabrication;
fabrication;(a)
(a)exfoliation
exfoliationofofTi
Ti3AlC 2 via etching with HF;
3 AlC2 via etching with HF;
(b)
(b)delamination
delaminationwith withTBAOH;
TBAOH;(c) (c)modifying
modifyingthe theglassy
glassycarbon
carbonelectrode
electrodewith
withMXene;
MXene;(d) (d)loading
loadingof
of
glucose
glucoseoxidase
oxidase(GOx),
(GOx),and;
and;(e)
(e)cross-linking
cross-linkingglutaraldehyde
glutaraldehyde(GTA)
(GTA)with
withGOx;
GOx;(f) (f)glucose
glucosedetection
detection
mechanism
mechanismof ofthe
theproposed
proposedbiosensing
biosensingsystem.
system.(B)
(B)Chronoamperometry
Chronoamperometrydata data(a)(a)and
andcalibration
calibrationplot
plot
(b) for Ti3 C2 –HF/TBA-based electrochemical glucose biosensor conducted using FcMeOH(2(2mM)
(b) for Ti3 C2 –HF/TBA-based electrochemical glucose biosensor conducted using FcMeOH mM)inin
pH
pH7.2
7.2PBS
PBS(electrolyte)
(electrolyte)and
and0.15
0.15VVpotential
potential(reproduced
(reproduced with
with permission
permission fromfrom reference
reference [64]).
[64]).
Sensors 2020, 20, x FOR PEER REVIEW 6 of 19
Other works explored hybrid configurations that combine the layered structure of MXenes with
the properties of other materials to add additional functions. Gu et al. constructed a porous
MXene-graphene (MG) nanocomposite-based glucose biosensor [66]. The 3D porous nanostructure
was prepared using a mixing-drying process in which the size of the pores was controlled by tuning
the content of Ti3C2 and graphene. The synthetic methodology and the preparation process of the
sensor are displayed in Figure 4. The porous structure provided more open structures to embed GOx
within the internal pores, favoring retention of the GOx activity. The biosensor exhibited good
electrocatalytic properties towards glucose biosensing for the detection of glucose in human sera.

Figure 4. Preparation of (A) Ti

Ti33C22TTxx MNS;
MNS; (B)
(B) pure
pure Ti
Ti33C
C22TTxxfilm,
film,pure
puregraphene
graphenefilm,
film, and
and MG
MG hybrid
film for enzyme immobilization (reproduced with with permission
permission from from reference
reference [66]).
[66]).

Other improvements have been achieved by decorating the surface of MXenes with metal oxide
nanoparticles (NPs), further increasing the surface area and conductivity of the electrodes and
maximizing the enzyme loading. A composite of Nafion-Au NPs-MXene was reported as electrode
material for the immobilization of GOx and subsequent detection of glucose [67]. The synergistic
Sensors 2020, 20, 5434 7 of 19

Wang et al. reported a mediator free biosensor for the detection of H2O2 by immobilizing
hemoglobin (Hb) on an MXene modified electrode [69]. The use of MXene lowered the LOD
of the sensor to the nM range. A similar type of Hb-MXene based biosensor was reported for the
electrochemical detection of nitrite using cyclic voltammetry [70]. Kai et al. modified the MXene surface
with horseradish peroxidase (HRP) to fabricate an electrochemical biosensor for the detection of H2 O2 .
The HRP enzyme was immobilized on an MXene/chitosan/GCE electrode, and the film demonstrated
good electrocatalytic activity toward the reduction of H2 O2 . The amperometric biosensor displayed
a wide linear range from 5 to 1650 µmol. L−1 , LOD of 0.74 µmol. L−1 and good operation stability.
The biosensor was successfully applied for the sensing of H2 O2 traces in food samples [71].
MXene composites were also used to develop biosensors used for the ultra-sensitive detection
of phenol in real water samples. These sensors are based on the use of the Tyrosinase (Tyr)
enzyme entrapped within a chitosan composite that increased the adhesion of MXene-Tyr onto
the GCE. The mechanism for phenol detection involves the oxidation of phenol by Tyr into the
corresponding o-quinone. Afterward, the electrochemical reduction of the o-quinone producing
polyhydric phenol is measured electrochemically. A noticeable increase in the current vs. time
was observed with increasing the concentration of phenol. The sensitivity of Tyr-MXene-Chi/GC
(414.4 mA M−1 ) was about 1.5 times higher than that of Tyr-Chi/GC (290.8 mA M−1 ). The LOD was
12 nmol L−1 while the linear range was from 5.0 × 10−8 to 15.5 × 10−6 mol L−1 [4].
Other sensor configurations reported the use of MXene as a transducer for the detection of
organophosphorus pesticides (OPs). Zhou and his coworkers reported an acetylcholinesterase
(AChE) based sensor for the detection of malathion using Ti3 C2 nanosheets and chitosan as an
immobilization matrix. The electrochemical behavior of the AChE/CS-Ti3 C2 /GCE biosensor was studied
by cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The biosensor displayed
excellent performance against malathion with a LOD as low as 0.3 × 10−14 M [72]. In another report,
the same analyte, i.e., malathion was detected by AChE inhibition, using Ag modified MXene as
a transducer. The modification of MXene with Ag NPs amplified the electrochemical signal; a LOD of
3.27 × 10−15 M was reported in this case [73].
Another configuration was adopted to design a biosensor for OPs by combining
Ti3 C2 MXene nanosheets with metal-organic frameworks (MOFs). The combined material,
a MOF-derived MnO2 /Mn3 O4 , Ti3 C2 MXene/Au NPs composite, was used as an electrochemical
biosensing platform with immobilized AChE enzyme, constructed as shown in Figure 5.
The vertically aligned, highly ordered nanosheets of Mn-MOF derived 3D MnO2 /Mn3 O4 combined
with MXene/Au NPs yielded a synergistic amplification effect, providing enlarged specific surface
area and good environmental biocompatibility. Using this biosensor, the detection of methamidophos
was achieved over a broad concentration range (10−12 –10−6 M). TheLOD (1.34 × 10−13 M) of the
biosensor far exceeds the maximum residue limits (MRLs) for methamidophos (0.01 mg/kg) established
by European Union [74]. Applicability of several of these enzyme-based MXene biosensors has
been tested for food quality analysis. A Ti3 C2 based double enzyme biosensor was reported for the
detection of inosine monophosphate (IMP), which imparts flavor to the meat and can be used as an
indicator to assess meat quality [75]. The developed biosensor was based on a nanohybrid structure
consisting of Ti3 C2 MXene as a highly conductive and stable base material, modified with two enzymes
(50 -nucleotidase and xanthine oxidase) and a core-shell bimetallic nanoflower composed of an Au core
and a Pt shell. In this configuration, the MXene provided a stable biocompatible microenvironment for
enzyme loading, while the double-enzyme was used to hydrolyze IMP to produce H2 O2 , which can
be easily determined electrochemically through the bimetallic nanoflowers. Therefore, the content of
IMP was indirectly quantified by monitoring the current change due to H2 O2 production. The LOD
achieved by this double enzyme biosensor was 2.73 ng mL−1 with a correlation coefficient of 0.9964
and a linear range between 0.04 and 17 g L−1 .
with immobilized AChE enzyme, constructed as shown in Figure 5. The vertically aligned, highly
ordered nanosheets of Mn-MOF derived 3D MnO2/Mn3O4 combined with MXene/Au NPs yielded a
synergistic amplification effect, providing enlarged specific surface area and good environmental
biocompatibility. Using this biosensor, the detection of methamidophos was achieved over a broad
concentration range (10−12–10−6 M). TheLOD (1.34 × 10−13 M) of the biosensor far exceeds the maximum
Sensors 2020, 20, 5434 8 of 19
residue limits (MRLs) for methamidophos (0.01 mg/kg) established by European Union [74].

Figure
Figure 5.5. Illustration of of
thethe
formation of of
MnO 2/Mn 3O4 composite (A), MXene/Au NPs (B), the
Illustration formation MnO 2 /Mn3 O4 composite (A), MXene/Au NPs (B),
fabrication process of AChE-Chit/MXene/Au NPs/MnO 2/Mn 3O4/GCE biosensor for methamidophos
the fabrication process of AChE-Chit/MXene/Au NPs/MnO 2 /Mn3 O4 /GCE biosensor for methamidophos
assay
assay (C)
(C) (reproduced
(reproduced with
with permission
permission from
from reference [74]).
reference [74]).

3.2. MXenes Based Electrochemical

Applicability Immunosensors
of several of these enzyme-based MXene biosensors has been tested for food
quality analysis. A Ti 3C2 based double enzyme biosensor was reported for the detection of inosine
Immunosensors combining immunochemical reactions based on the antibody (Ab)-antigen
monophosphate
(Ag) recognition (IMP),
with anwhich impartselectrochemical
appropriate flavor to the meat and canprovide
transducer be usedsignificant
as an indicator to assess
advantages for
meat quality [75]. The developed biosensor was based on a nanohybrid structure consisting
bioanalysis, including cost-effectiveness, low reagent and sample volume, portability, high-specificity of Ti3C2
MXene as a highly
and sensitivity, andconductive and stable
high-throughput base material,
analysis modified with two
[76]. Immunosensors haveenzymes (5′-nucleotidase
applications in various
and xanthine oxidase) and a core-shell bimetallic nanoflower composed of an Au
fields of analysis, such as clinical medicine [77,78], environmental pollutant evaluation core and a Pt shell.
[79–81],
In this configuration, the MXene provided a stable biocompatible microenvironment for
food inspection [82,83], and pathogenic microorganism detection [84,85]. The incorporation of MXenes enzyme
loading, while theof
in the fabrication double-enzyme
immunosensors was used to
provide hydrolyze IMP
opportunities for to producebioactivity
increasing H2O2, which of can be easily
immobilized
determined electrochemically through the bimetallic nanoflowers. Therefore, the content
Abs on electrode surfaces, increasing surface area, and improving detection sensitivity. Kumar et of IMP wasal.
indirectly quantified by monitoring the current change due to H 2O2 production. The LOD achieved
fabricated an immunosensor for the detection of carcinoembryonic antigen (CEA) [62], an important
cancer biomarker found in the liver, breast, lung, colorectal, ovarian, and pancreatic cancer patients.
To fabricate the sensor, amino-functionalized Ti3 C2 MXene was used to chemically immobilize -COOH
terminated-CEA. The electrochemical detection mechanism of the sensors is shown in Figure 6.
The MXenes were synthesized using a layer delamination method that reduces the surface defects in
the MXene and produces MXene nanoflakes with higher electrical conductivity. The biosensor showed
a linear detection range of 0.0001 to 2000 ng mL−1 with a sensitivity of 37.9 µA ng−1 mL cm−2 and
a stability up to 7 days. Recovery studies for the quantification of CEA in serum samples indicated
promising results.
Another MXene based CEA biosensor has been reported using a sandwich-type immunoassay
format in which Ti3 C2 was first functionalized with amino silane (APTES) for covalent immobilization
of monoclonal anti-CEA antibodies (Ab1 ) with surface plasmon resonance (SPR) detection.
A MXene-hollow Au NPs (HGNPs) nanohybrid was synthesized and further decorated with
staphylococcal protein A (SPA) to immobilize the polyclonal anti-CEA detection antibody (Ab2)
and serve as signal enhancers. The capture of CEA resulted in the formation of an Ab2-conjugated
SPA/HGNPs/N-Ti3C2-MXene sandwiched nanocomplex on the SPR chip and the generation of a
response signal. This SPR immunoassay had a reported LOD of 0.15 fM and a linear range of 0.001 to
1000 pM.
to chemically immobilize -COOH terminated-CEA. The electrochemical detection mechanism of the
sensors is shown in Figure 6. The MXenes were synthesized using a layer delamination method that
reduces the surface defects in the MXene and produces MXene nanoflakes with higher electrical
conductivity. The biosensor showed a linear detection range of 0.0001 to 2000 ng mL−1 with a
Sensors 2020, 20,
sensitivity of 5434 9 of 19
37.9 µ A ng−1 mL cm−2 and a stability up to 7 days. Recovery studies for the quantification
of CEA in serum samples indicated promising results.

Figure 6.
Figure 6. Schematic of the
the electrochemical
electrochemical carcinoembryonic
carcinoembryonic antigen
antigen (CEA)
(CEA) detection
detection mechanism
mechanism
(reproduced with
(reproduced with permission
permissionfrom
fromreference
reference[62]).
[62]).

In other configurations,
Another MXene based CEA Chenbiosensor
et al. developed
has beena Ti 3 C2 MXene-based
reported interdigitated
using a sandwich-type capacitance
immunoassay
immunosensor for the detection of prostate-specific antigen (PSA), an important
format in which Ti3C2 was first functionalized with amino silane (APTES) for covalent immobilization biomarker for used
to
of screen prostate
monoclonal cancer. antibodies
anti-CEA The normal(Ab levels
1) withof PSA in the
surface serum of
plasmon healthy males
resonance (SPR) are less than
detection. A
4.0 ng mL−1 , whereas
MXene-hollow Au NPs rising levels are
(HGNPs) associated was
nanohybrid with synthesized
prostate cancer. andThe biosensor
further utilized
decorated an
with
MXene modifiedprotein
staphylococcal interdigitated
A (SPA)micro comb electrode
to immobilize to immobilize
the polyclonal anti-CEAanti-PSA capture
detection Ab, whereas
antibody (Ab2) andAu
NPs
serve functionalized
as2020,
Sensors signal FOR with
20, x enhancers. horseradish
The capture
PEER REVIEW peroxidase (HRP) and
of CEA resulted in detection
the formationantibody
of anwere used9 as
Ab2-conjugated the
of 19
signal-transducer
SPA/HGNPs/N-Ti3C2-MXene tags. To further increase the
sandwiched sensitivity ofon
nanocomplex thetheassay,
SPRa chip
tyramine
and signal amplification
the generation of a
andsignal-transducer
enzymatic tags. To further increase the sensitivity of the assay, a tyramine signal amplification
response signal.biocatalytic precipitationhad
This SPR immunoassay were coupledLOD
a reported withofthe 0.15main
fM andimmunochemical
a linear range ofreaction.
0.001 to
and enzymatic biocatalytic precipitation were coupled with the main immunochemical reaction. Under
Under
1000 pM. optimum conditions, the change of the immunosensor in the capacitance increased with
optimum conditions, the change of the immunosensor in the −1 capacitance increased with the increasing
the increasing target PSA concentrations
In other configurations, from
Chen et al. developed 0.1 ng
a TimL to 50 ng mL−1
3C2 MXene-based at a detection
interdigitated limit of
capacitance
target PSA −1concentrations from 0.1 ng mL −1 to 50 ng mL−1 at a detection limit of 0.031 ng mL−1. The
0.031 ng mL . The
immunosensor characteristics
for the detection ofof the developed system
prostate-specific antigenare shown
(PSA), an in Figure 7.biomarker
important Despite these merits,
for used to
characteristics of the developed system are shown in Figure 7. Despite these merits, one of the
one of the
screen limitations
prostate cancer.ofThethis immunosensor
normal levels of PSA is the complex
in the serum fabrication procedure
of healthy males are lessand long
than 4.0 reaction
ng mL−1,
limitations of this immunosensor is the complex fabrication procedure and long reaction time as
time as compared
whereas rising to commercial
levels are associatedenzyme-linked
with prostate immunosorbent
cancer. assays assays [86].
The biosensor utilized an MXene modified
compared to commercial enzyme-linked immunosorbent [86].
interdigitated micro comb electrode to immobilize anti-PSA capture Ab, whereas Au NPs
functionalized with horseradish peroxidase (HRP) and detection antibody were used as the

Figure
Figure 7. 7.Analytical
Analytical performance
performanceofofthethe developed immunoassay
developed (A) capacitance
immunoassay responses
(A) capacitance of Ti3C2 of
responses
MXene-based interdigitated immunosensor toward target PSA standards; (B) the corresponding
Ti3 C2 MXene-based interdigitated immunosensor toward target PSA standards; (B) the corresponding
calibration
calibration plots;
plots; andand
(C)(C)
the the specificity
specificity of capacitance
of capacitance immunosensor
immunosensor against
against target
target PSAPSA and non-
and non-targets
targets including AFP, CEA, and CA 125 (reproduced with permission
including AFP, CEA, and CA 125 (reproduced with permission from reference [86]).from reference [86]).

3.3.3.3.
DNA/Aptamer Based
DNA/Aptamer BasedBiosensor
Biosensor
Biosensors
Biosensors withnucleic
with nucleicacid
aciddetection
detection using
using either
either optical
optical or
orelectrical
electricaloutput
outputtotomonitor
monitorthethe
hybridization
hybridization event
event havebeen
have beenwidely
widelyreported
reported as bioanalytical
bioanalyticalplatforms
platformsfor
formany applications
many [87].
applications [87].
Recently, MXenes have been explored as an electrode material to monitor the hybridization
Recently, MXenes have been explored as an electrode material to monitor the hybridization event event
andand enhance
enhance detectionsensitivity.
detection sensitivity. Zheng
Zheng etet al.
al. reported
reportedaa DNA/Pd/Pt
DNA/Pd/Ptnanocomposite
nanocompositeforforthethe
electrochemical
electrochemical detectionofofdopamine
detection dopamine(DA) (DA) [88],
[88], an
an important
important catecholamine
catecholamineneurotransmitter
neurotransmitter in in
living organisms that plays an essential role in the function of human renal, metabolism,
living organisms that plays an essential role in the function of human renal, metabolism, cardiovascular,
cardiovascular, and central nervous systems [89]. Abnormal DA levels may indicate neurological
disorders and a variety of acute and chronic diseases such as Schizophrenia, Parkinson, and
Alzheimer [90]. In the developed biosensor, MXene nanosheets act as a matrix for the loading of the
DNA and Pd/Pt. First, the DNA was adsorbed on the MXene surface through π-π stacking interaction
between the nucleotide bases and MXene nanosheets, then the Pd and Pt NPs were synthesized
Sensors 2020, 20, 5434 10 of 19

and central nervous systems [89]. Abnormal DA levels may indicate neurological disorders and a
variety of acute and chronic diseases such as Schizophrenia, Parkinson, and Alzheimer [90]. In the
developed biosensor, MXene nanosheets act as a matrix for the loading of the DNA and Pd/Pt. First,
the DNA was adsorbed on the MXene surface through π-π stacking interaction between the nucleotide
bases and MXene nanosheets, then the Pd and Pt NPs were synthesized in-situ in the presence of
DNA/MXene nanocomposite. The results revealed that the presence of DNA prevents the restacking of
Ti3 C2 nanosheets and facilitates the even growth of PdNPs and Pd/Pt NPs. Moreover, the deposition of
Pd/Pt NPs onto Ti3 C2 nanosheets enhanced the electrocatalytic activity of the nanocomposites towards
DA. In the final step, a GCE electrode was modified with the DNA/MXene/NPs composite to create the
DA biosensor. The amperometric biosensor exhibited DA detection capabilities in concentration range
of 0.2 to 1000 µM with a LOD of 30 nM (S/N = 3) and high selectivity against uric acid, ascorbic acid,
and glucose [88].
The detection of specific DNA sequences is significant, not only in clinical diagnostics but also
in the environment and food analysis fields. Wang and his coworkers developed a nanobiosensor
for gliotoxin [84], one of the most toxic mycotoxins produced by Aspergillus fumigatus, which poses
a serious threat to humans and animals health. The biosensor was prepared by modifying MXene
nanosheets with a tetrahedral DNA nanostructure (TDN), which acts as the main sensing element.
The stated benefits of incorporating MXenes in the sensor design included increasing the sensitivity and
providing an ample surface area for immobilizing a much greater amount of TDN onto the electrode.
Moreover, the titanium element on the surface of MXene nanosheets offers a facile method for assembly
via strong chelation interaction between the titanium and phosphate groups of TDNs, thus eliminating
the need for complex and costly chemical modification of TDNs, which is generally required for the
immobilization of TDNs onto the electrode. The amperometric response of the optimized biosensor
responded to gliotoxin concentrations increasing from 5 pM to 10 nM, with an LOD of 5 pM. Zhoe et al.
reported an impedimetric aptasensor for electrochemical detection of osteopontin (OPN), a cancer
biomarker that is also responsible for tumor growth and progression in human cervical cancer.
The aptasensor was based on Ti3 C2 MXene-phosphomolybdic acid (PMo12 )-polypyrrole (PPy)
nanohybrid used as an immobilization matrix for the anti-OPN aptamer. The fabrication procedure
of the developed aptasensor is represented in Figure 8. The PPy@Ti3 C2 /PMo12 -based aptasensor
exhibited high selectivity and stability along with an extremely low detection limit of 0.98 fg mL−1 ,
and applicability in human serum samples [63].
Apart from its use as transducer surface in electrochemical biosensors, MXenes have also been used
as bioimmobilization material or quencher in optical DNA assays. For example, Peng et al. designed
an “off-on” fluorescent biosensor for the detection of Human papillomavirus (HPV) infection [91].
HPV is a human pathogen known to induce cervical cancer, the second most common cancer in
women [92]. The assay was designed based on a fluorescence quenching mechanism, which has
already been used in various fluorescence-based biosensors [93]. A fluorescent dye (FAM) labeled
ssDNA was used as a fluorescent probe while Ti3 C2 MXene was used as a nanoquencher. In the
presence of Ti3 C2, the fluorescence of the FAM tagged ssDNA probe (P) was completely quenched
while after interacting with its complementary DNA target (T), a P/T hybridized dsDNA structure
is formed, which resulted in the recovery of the fluorescence signal. Furthermore, Exonuclease III
(Exo III) was used to improve the sensitivity by enhancing fluorescence. Interestingly, when Exo III
was introduced in the hybridization process, the 30 end of the newly formed dsDNA was recognized
by the Exo III, and then the hydrolysis of the P/T complex was initiated. This cycling process facilitated
by the Exo III enhanced the fluorescence of P/T lowering the limit for HPV-18 detection to 100 pM [91].
 LOD of 5 pM. Zhoe et al. reported an impedimetric aptasensor for electrochemical detection of
osteopontin (OPN), a cancer biomarker that is also responsible for tumor growth and progression in
human cervical cancer. The aptasensor was based on Ti3C2 MXene-phosphomolybdic acid
(PMo12)-polypyrrole (PPy) nanohybrid used as an immobilization matrix for the anti-OPN aptamer.
The fabrication procedure of the developed aptasensor is represented in Figure 8. The
Sensors 20,2/PMo
2020,3C
PPy@Ti 5434 12-based aptasensor exhibited high selectivity and stability along with an extremely
11 of 19
low detection limit of 0.98 fg mL , and applicability in human serum samples [63].
−1

Figure 8. Schematic diagram of the aptasensor fabrication based on PPy@Ti3C2/PMo12 for the OPN
Figure 8. Schematic diagram of the aptasensor fabrication based on PPy@Ti3 C2 /PMo12 for the
detection. (reproduced with permission from reference [63]).
OPN detection. (reproduced with permission from reference [63]).

Apart from
Utilizing MXenes its use
asas transducer surface
a nanoquencher, Zhang in electrochemical biosensors,
et al. designed MXenesresonance
a fluorescence have also been
energy
used as bioimmobilization material or quencher in optical DNA assays. For example,
transfer (FRET) bioassay for the detection of exosomes (Figure 9). This platform is based on a Cy3
Peng et al. designed an “off-on” fluorescent biosensor for the detection of Human papillomavirus
dye-labeled CD63 aptamer (Cy3-CD63 aptamer)/Ti3 C2 MXenes nanocomplex in which the fluorescence
(HPV) infection [91]. HPV is a human pathogen known to induce cervical cancer, the second most
of the dye was quenched by the MXene nanosheets, while the addition of exosomes in the reaction
common cancer in women [92]. The assay was designed based on a fluorescence quenching mechanism,
mixture immediately recovered the fluorescence. The turn-on fluorescence phenomenon was ascribed
which
Sensors has
2020, 20,already
x FOR PEER been used in various fluorescence-based biosensors [93]. A fluorescent dye (FAM)
REVIEW 11 of 19
to labeled
the release of the Cy3-CD63 aptamer from the surface of MXenes because of the relative strong
ssDNA was used as a fluorescent probe while Ti3C2 MXene was used as a nanoquencher. In the
specific
relative
presencerecognition
strong
of Ti3specific
C2, thebetween the aptamer
recognition
fluorescence andtagged
of between
the FAM theaptamer
the CD63
ssDNA protein
and on
the
probe exosomes.
(P)CD63 Theon
protein
was completely assay achieved
exosomes.
quenched whileThea
LOD 1.4 × 10 3 particles mL−1 , which is reported as 1000× lower than the conventional ELISA based
assay
afterachieved a LOD
interacting with 1.4 × 10 particles mL
3
its complementary −1
DNA , which is reported
target (T), as 1000×dsDNA
a P/T hybridized lower than the conventional
structure is formed,
assay
ELISA
which[94].
based assay
resulted in [94].
the recovery of the fluorescence signal. Furthermore, Exonuclease III (Exo III) was
used to improve the sensitivity by enhancing fluorescence. Interestingly, when Exo III was introduced
in the hybridization process, the 3′ end of the newly formed dsDNA was recognized by the Exo III, and
then the hydrolysis of the P/T complex was initiated. This cycling process facilitated by the Exo III
enhanced the fluorescence of P/T lowering the limit for HPV-18 detection to 100 pM [91].
Utilizing MXenes as a nanoquencher, Zhang et al. designed a fluorescence resonance energy
transfer (FRET) bioassay for the detection of exosomes (Figure 9). This platform is based on a Cy3
dye-labeled CD63 aptamer (Cy3-CD63 aptamer)/Ti3C2 MXenes nanocomplex in which the
fluorescence of the dye was quenched by the MXene nanosheets, while the addition of exosomes in
the reaction mixture immediately recovered the fluorescence. The turn-on fluorescence phenomenon
was ascribed to the release of the Cy3-CD63 aptamer from the surface of MXenes because of the

Figure 9. Schematic
Schematic illustration
illustration of
of the
the developed
developed fluorescence
fluorescence resonance
resonance energy (FRET)-based
aptasensor (reprinted with permission from reference
reference [94]).
[94]).

3.4. MXene for Next Generation Wearable Biosensors

Wearable electronics attracted considerable attention since the commercialization of
smartphones and other portable health monitoring devices due to their ability to provide substantial
information regarding the health of an individual. Early research in this field focused on the
development of physical sensors that could monitor the heart rate, oxygen level, movement such as
steps and calories burned, etc., but in the last years, the focus broadened to tackle challenges in health
care applications such as monitoring of disease biomarkers. The high specificity, portability, and low
Sensors 2020, 20, 5434 12 of 19

3.4. MXene for Next Generation Wearable Biosensors

Wearable electronics attracted considerable attention since the commercialization of smartphones
and other portable health monitoring devices due to their ability to provide substantial information
regarding the health of an individual. Early research in this field focused on the development
of physical sensors that could monitor the heart rate, oxygen level, movement such as steps and
calories burned, etc., but in the last years, the focus broadened to tackle challenges in health care
applications such as monitoring of disease biomarkers. The high specificity, portability, and low
power consumption of wearable biosensing devices hold promise for such applications. These include
biosensor platforms for noninvasive analysis of biofluids, such as interstitial fluid (ISF), sweat, saliva,
or tears. These fluids have been targeted mostly because of the advantage of noninvasive sampling,
minimizing the risk of infection during the sampling procedure and user-friendly operation.
Key characteristics when designing wearable devices are the flexibility, mechanical properties,
and conductivity of the material used as a sensing platform. Challenges include the integration
and scalability of the bioelectronics components in order to achieve the maximum performance in
an accurate and sensitive manner and ensure manufacturability. Large surface area nanomaterials
have been explored as materials for flexible sensors to increase the effective contact area and impart
favorable electrical and mechanical properties. MXenes represent a new wave of materials for
wearable sensors and biosensors. The main applications explored thus far include pressure and
strain sensors [95], piezoresistive sensors [96], and chemical sensors for detection of subtle pressure,
simultaneous monitoring of human activities, quantitative illustration of pressure distribution,
human-computer interaction, and electronic skin. The incorporation of MXenes in conjunction
with biomolecules for wearable applications is relatively unexplored but rapidly emerging.
Cheng et al. used MXene to fabricate a piezoresistive sensor with spinous microstructures inspired
by the human skin, which can be considered a sensitive biological sensor. The sensor was prepared
using a simple abrasive paper stencil printing method. The spinous microstructures effectively
increased contact area of the conductive channels, consequently improving the performance of the
pressure sensor: Low-pressure detection limit (4.4 Pa), fast response time (<130 ms), high sensitivity
(151.4 kPa−1 ), and excellent stability over 10,000 cycles [97]. Guo et al. presented a similar kind
of flexible, highly sensitive, and degradable pressure sensor. A porous MXene-impregnated tissue
paper was sandwiched between an interdigitated electrode-coated PLA thin sheet and a biodegradable
polylactic acid (PLA) thin sheet. The flexible sensor exhibited high sensitivity (10.2 Pa), fast response
(11 ms), low power consumption (10–8 W), biodegradability, and excellent reproducibility over
10,000 cycles [98]. Li and Du reported an MXene-Ag nanocomposite based sensitive strain sensor.
The sensor is based on 1D Ag nanowires, 0D Ag NPs and 2D MXene nanosheets. The Ag NPs act as a
bridge between the MXene sheets and the Ag nanowires. This design helped to increase the elasticity
and conductivity of the sensor. This fabric-based strain sensor was composed of elastic textile material
(double-covered yarn) that was doped and blended with Ag/MXene nanocomposite, creating a wearable
clothing material. The as-prepared sensor showed highly sensitive and stretchable performance with a
high gauge factor at an exceptionally large strain (350%). In addition to wearable textiles, the developed
sensor has potential applications in biomedical and fire safety applications [99]. Other configurations
use MXene in conjunction with hydrogels to produce wearable sensors [100,101].
Apart from these physical sensors, Lei et al. have developed an MXene-based wearable biosensor
for sweat analysis. The device was fabricated by using 2D MXene (Ti3 C2 Tx ) nanosheets as material to
develop an oxygen-rich enzyme biosensor for H2 O2 detection based on a Ti3 C2 Tx /PB (Prussian Blue)
composite and enzyme. Due to the high conductivity and excellent electrochemical activity of
exfoliated MXene, Ti3 C2 Tx /PB composites showed better electrochemical performance compared to
carbon nanotubes/PB and graphene/PB composites toward H2 O2 detection. The sensing device contains
a versatile replaceable sensor component, which can be inserted and changed with customized sensors
prepared to track different analytes, i.e., glucose, lactate, or pH value (Figure 10). The substrate of the
device was composed of superhydrophobic carbon fiber that was used to create a tri-phase interface and
material to develop an oxygen-rich enzyme biosensor for H2O2 detection based on a Ti3C2Tx/PB
(Prussian Blue) composite and enzyme. Due to the high conductivity and excellent electrochemical
activity of exfoliated MXene, Ti3C2Tx/PB composites showed better electrochemical performance
compared to carbon nanotubes/PB and graphene/PB composites toward H2O2 detection. The sensing
device2020,
Sensors contains
20, 5434a versatile replaceable sensor component, which can be inserted and changed 13with
of 19
customized sensors prepared to track different analytes, i.e., glucose, lactate, or pH value (Figure 10).
The substrate of the device was composed of superhydrophobic carbon fiber that was used to create
protect the connector from sweat corrosion. The sensing performance of the as-prepared device was
a tri-phase interface and protect the connector from sweat corrosion. The sensing performance of the
evaluated using artificial sweat. Electrochemical results showed sensitivities of 11.4 µA mm−1 cm−2
as-prepared device was evaluated using artificial sweat. Electrochemical results showed sensitivities
for lactate 35.3 µA mm−1 cm−2 for glucose. Furthermore, the sensor was tested on human subjects and
of 11.4 µA mm−1 cm−2 for lactate 35.3 µA mm−1 cm−2 for glucose. Furthermore, the sensor was tested
used for sweat analysis. The obtained results showed simultaneous measurements of glucose and
on human subjects and used for sweat analysis. The obtained results showed simultaneous
lactate with high sensitivity and repeatability [102].
measurements of glucose and lactate with high sensitivity and repeatability [102].

Figure 10.
Figure 10.Schematic
Schematic diagram
diagram of wearable
of wearable sweat
sweat sensor sensor with
(reprinted (reprinted with
permission permission
from from
reference [102]).
reference [102]).
4. Conclusions and Future Prospects
4. Conclusions and Future Prospects
In summary, MXenes are an emerging class of 2D nanomaterials mainly composed of transition
metalIncarbides,
summary, MXenes
nitrides, or are an emerging
carbonitrides. class ofhave
MXenes 2D nanomaterials mainly
gained substantial composed
attention of transition
in fields such as
metal carbides,
batteries nitrides, or carbonitrides.
and supercapacitors, MXenes have
and their application in gained
chemicalsubstantial attention
and biological in fields
sensors such as
is growing.
This paper provided an overview of the MXenes properties and their incorporation in the development
of enzyme, antibodies, and aptamer-based bioanalytical sensors. As compared to the previously
discovered 2D nanomaterials, MXenes possess some superior characteristics such as hydrophilicity,
ease of functionalization, high electron transport capability, and vast compositional variety, high surface
area due to their “accordion-like” morphology, and biocompatibility, which makes them attractive for
biosensing applications. The surface terminal functional groups such as -O, -OH, -F are amenable to
functionalization with biomolecules and enable the development of innovative bioanalytical platforms.
A growing area is to incorporate MXene in wearable technologies and devices that have the
required stability, flexibility, and targeting properties to be interfaced with the human body. This area is
expected to grow in the future with new developments in processing, integration, and manufacturing.
Several challenges need to be addressed in order to utilize the full potential of this novel class
of materials. (1) Current synthetic methods to create MXenes involve the use of HF as an etchant.
The method is not environmentally-friendly and it cannot be easily scaled up, thus hindering production
at a commercial scale. Other mild etchants such as LiF/HCl, molten ZnCl2 have also been reported,
but the final yield is very low. Significant progress is needed to advance the sustainable and scalable
Sensors 2020, 20, 5434 14 of 19

synthesis of MXenes. Moreover, a large number of MXenes have been predicted theoretically, but
only a few have been actually produced by exfoliating MAX phases. Thus, it is important to shift
the synthesis procedure from theoretical prediction to wet chemical labs. (2) The HF based etching
method produces MXenes with randomly functionalized surfaces and it is difficult to obtain MXenes
with specific and uniformly distributed surface termination. (3) The presence of fluorine on the surface
hinders the use of MXenes in biomedical applications or for the immobilization of biomolecules.
Therefore, new fluorine-free synthesis routes with high yield need to be developed, or these groups
should be removed from the surface. (4) The top-down synthesis gives less control over tuning
the morphology and surface modification of the MXenes. Hence, a bottom-up synthesis approach
of MXenes should be developed as an alternative. (5) The long-time sonication for delamination
produces MXenes with high surface defects that could possibly alter the properties of MXenes.
Additionally, organic solvents are being used for intercalation and delamination, which is also not a
very environmentally friendly approach. (6) Lastly, the oxidation of MXenes in oxygenated solvents is a
major obstacle. Other approaches are needed to make it possible to use MXenes in the anodic potential
window without compromising the inherent physicochemical properties of MXenes. Looking ahead,
more effective synthesis and surface modification strategies are required to advance application of
MXene in the development of practical bioanalytical sensors and other applications. Scalability in
synthesis and processing as well as integration and more effective transduction, are needed to ensure
future growth and implementation of these materials in wearable sensing applications.

Author Contributions: R.K. contributed with literature review, writing, original draft preparation and selection
of the relevant scientific literature. S.A. contributed with review and editing, supervision, project administration
and funding acquisition. All authors have read and agreed to the published version of the manuscript.
Funding: This work was funded by the National Science Foundation under Grant No. 1561491.
Acknowledgments: This work was funded by the National Science Foundation under Grant No. 1561491.
Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s)
and do not necessarily reflect the views of the National Science Foundation. Reem Khan gratefully acknowledges
the Higher Education Commission (HEC) of Pakistan and the US-Pakistan Knowledge Corridor Program for
support of her studies at Clarkson University.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Hantanasirisakul, K.; Gogotsi, Y. Electronic and Optical Properties of 2D Transition Metal Carbides and
Nitrides (MXenes). Adv. Mater. 2018, 30, 1804779. [CrossRef] [PubMed]
2. Naguib, M.; Mashtalir, O.; Carle, J.; Presser, V.; Lu, J.; Hultman, L.; Gogotsi, Y.; Barsoum, M.W.
Two-Dimensional Transition Metal Carbides. ACS Nano 2012, 6, 1322–1331. [CrossRef] [PubMed]
3. Sun, Z.M. Progress in research and development on MAX phases: A family of layered ternary compounds.
Int. Mater. Rev. 2011, 56, 143–166. [CrossRef]
4. Mashtalir, O.; Naguib, M.; Mochalin, V.; Dall’Agnese, Y.; Heon, M.; Barsoum, M.W.; Gogotsi, Y.
Intercalation and delamination of layered carbides and carbonitrides. Nat. Commun. 2013, 4, 1716.
[CrossRef] [PubMed]
5. Zhu, J.; Ha, E.; Zhao, G.; Zhou, Y.; Huang, D.; Yue, G.; Hua, L.; Sun, N.; Wang, Y.; Lee, L.Y.S.; et al.
Recent advance in MXenes: A promising 2D material for catalysis, sensor and chemical adsorption.
Co-Ord. Chem. Rev. 2017, 352, 306–327. [CrossRef]
6. Alhabeb, M.; Maleski, K.; Anasori, B.; Lelyukh, P.; Clark, L.; Sin, S.; Gogotsi, Y. Guidelines for
synthesis and processing of two-dimensional titanium carbide (Ti3 C2 Tx MXene). Chem. Mater. 2017,
29, 7633–7644. [CrossRef]
7. Huang, K.; Li, Z.; Lin, J.; Han, G.; Huang, P. Two-dimensional transition metal carbides and nitrides (MXenes)
for biomedical applications. Chem. Soc. Rev. 2018, 47, 5109–5124. [CrossRef]
8. Soleymaniha, M.; Shahbazi, M.-A.; Rafieerad, A.R.; Maleki, A.; Amiri, A. Promoting Role of MXene
Nanosheets in Biomedical Sciences: Therapeutic and Biosensing Innovations. Adv. Health Mater. 2018,
8, 1801137. [CrossRef]
Sensors 2020, 20, 5434 15 of 19

9. Gogotsi, Y.; Anasori, B. The Rise of MXenes. ACS Nano 2019, 13, 8491–8494. [CrossRef]
10. Sinha, A.; Dhanjai; Zhao, H.; Huang, Y.; Lu, X.; Chen, J.; Jain, R. MXene: An emerging material for sensing
and biosensing. TrAC Trends Anal. Chem. 2018, 105, 424–435. [CrossRef]
11. Zhang, Y.; Wang, L.; Zhang, N.; Zhou, Z. Adsorptive environmental applications of MXene nanomaterials:
A review. RSC Adv. 2018, 8, 19895–19905. [CrossRef]
12. Rasool, K.; Pandey, R.P.; Rasheed, P.A.; Buczek, S.; Gogotsi, Y.; Mahmoud, K.A. Water treatment and
environmental remediation applications of two-dimensional metal carbides (MXenes). Mater. Today 2019,
30, 80–102. [CrossRef]
13. Sinha, A.; Dhanjai; Mugo, S.M.; Chen, J.; Lokesh, K.S. Handbook of Nanomaterials in Analytical Chemistry;
MXene-based sensors and biosensors: Next-generation detection platforms; Elsevier: Amsterdam,
The Netherlands, 2020; pp. 361–372.
14. Chang, W.-C.; Cheng, S.-C.; Chiang, W.-H.; Liao, J.-L.; Ho, R.-M.; Hsiao, T.-C.; Tsai, D.-H. Quantifying Surface
Area of Nanosheet Graphene Oxide Colloid Using a Gas-Phase Electrostatic Approach. Anal. Chem. 2017, 89,
12217–12222. [CrossRef] [PubMed]
15. Chen, J.; Meng, H.; Tian, Y.; Yang, R.; Du, D.; Li, Z.; Qu, L.; Lin, Y. Recent advances in functionalized MnO2
nanosheets for biosensing and biomedicine applications. Nanoscale Horiz. 2018, 4, 321–338. [CrossRef]
16. Mohamed, H. Post-Synthetic Immobilization of Ni Ions in Porous-Organic Polymer-Graphene Composite
for the Non-Noble Metal Electrocatalytic Water Oxidation. Eur. Soc. J. Catal. 2017, 9, 2894.
17. Kim, J.; Han, J.; Seo, M.; Kang, S.; Kim, D.; Ihm, J. High-surface area ceramic-derived boron-nitride and its
hydrogen uptake properties. J. Mater. Chem. A 2013, 1, 1014–1017. [CrossRef]
18. Mateti, S.; Wong, C.S.; Liu, Z.; Yang, W.; Li, Y.; Chen, Y. Biocompatibility of boron nitride nanosheets.
Nano Res. 2017, 11, 334–342. [CrossRef]
19. Birch, M.E.; Ruda-Eberenz, T.A.; Chai, M.; Andrews, R.; Hatfield, R.L. Properties that influence the specific
surface areas of carbon nanotubes and nanofibers. Ann. Occup. Hyg. 2013, 57, 1148–1166. [CrossRef]
20. Ma, P.-C.; Siddiqui, N.A.; Marom, G.; Kim, J. Dispersion and functionalization of carbon nanotubes for
polymer-based nanocomposites: A review. Compos. Part A Appl. Sci. Manuf. 2010, 41, 1345–1367. [CrossRef]
21. Ouyang, M.; Huang, J.-L.; Cheung, C.L.; Lieber, C.M. Energy Gaps in “Metallic” Single-Walled
Carbon Nanotubes. Science 2001, 292, 702–705. [CrossRef]
22. Lakshmi, A.; Gracelin, D.L.; Vigneshwari, M.; Karpagavinayagam, P.; Veeraputhiran, V.; Vedhi, C.
Microwave Synthesis and Characterization of Multiwalled Carbon Nanotubes (MWCNT) and Metal
Oxide Doped MWCNT. J. Nanosci. Technol. 2015, 1, 19–22.
23. El Beqqali, O.; Zorkani, I.; Rogemond, F.; Chermette, H.; Ben Chaabane, R.; Gamoudi, M.; Guillaud, G.
Electrical properties of molybdenum disulfide MoS2 . Experimental study and density functional
calculation results. Synth. Met. 1997, 90, 165–172. [CrossRef]
24. Sobanska, Z.; Zapor, L.; Szparaga, M.; St˛epnik, M. Biological effects of molybdenum compounds in nanosized
forms under in vitro and in vivo conditions. Int. J. Occup. Med. Environ. Health 2020, 33, 1–19. [CrossRef]
[PubMed]
25. Ikram, M.; Liu, L.; Liu, Y.; Ma, L.; Lv, H.; Ullah, M.; He, L.; Wu, H.; Wang, R.; Shi, K. Fabrication and
characterization of a high-surface area MoS2 @WS2 heterojunction for the ultra-sensitive NO2 detection at
room temperature. J. Mater. Chem. A 2019, 7, 14602–14612. [CrossRef]
26. Mahmood, N.; De Castro, I.A.; Pramoda, K.; Khoshmanesh, K.; Bhargava, S.K.; Kalantar-Zadeh, K.
Atomically thin two-dimensional metal oxide nanosheets and their heterostructures for energy storage.
Energy Storage Mater. 2019, 16, 455–480. [CrossRef]
27. Jia, Z.; Wang, J.; Wang, Y.; Li, B.; Wang, B.; Qi, T.; Wang, X. Interfacial Synthesis of δ-MnO2 Nano-sheets
with a Large Surface Area and Their Application in Electrochemical Capacitors. J. Mater. Sci. Technol. 2016,
32, 147–152. [CrossRef]
28. Ren, C.E.; Zhao, M.-Q.; Makaryan, T.; Halim, J.; Boota, M.; Kota, S.; Anasori, B.; Barsoum, M.W.; Gogotsi, Y.
Porous Two-Dimensional Transition Metal Carbide (MXene) Flakes for High-Performance Li-Ion Storage.
ChemElectroChem 2016, 3, 689–693. [CrossRef]
29. Wang, H.; Wu, Y.; Zhang, J.; Li, G.; Huang, H.; Zhang, X.; Jiang, Q. Enhancement of the electrical
properties of MXene Ti3 C2 nanosheets by post-treatments of alkalization and calcination. Mater. Lett. 2015,
160, 537–540. [CrossRef]
Sensors 2020, 20, 5434 16 of 19

30. Naguib, M.; Kurtoglu, M.; Presser, V.; Lu, J.; Niu, J.; Heon, M.; Hultman, L.; Gogotsi, G.A.;
Barsoum, M.W. Two-Dimensional Nanocrystals Produced by Exfoliation of Ti3 AlC2 . Adv. Mater. 2011,
23, 4248–4253. [CrossRef]
31. Khazaei, M.; Ranjbar, A.; Arai, M.; Sasaki, T.; Yunoki, S. Electronic properties and applications of MXenes:
A theoretical review. J. Mater. Chem. C 2017, 5, 2488–2503. [CrossRef]
32. Lukatskaya, M.R.; Mashtalir, O.; Ren, C.E.; Dall’Agnese, Y.; Rozier, P.; Taberna, P.L.; Naguib, M.; Simon, P.;
Barsoum, M.W.; Gogotsi, Y. Cation Intercalation and High Volumetric Capacitance of Two-Dimensional
Titanium Carbide. Science 2013, 341, 1502–1505. [CrossRef] [PubMed]
33. Ghidiu, M.; Lukatskaya, M.R.; Zhao, M.-Q.; Gogotsi, Y.; Barsoum, M.W. Conductive two-dimensional
titanium carbide ‘clay’ with high volumetric capacitance. Nature 2014, 516, 78–81. [CrossRef] [PubMed]
34. Halim, J.; Lukatskaya, M.R.; Cook, K.M.; Lu, J.; Smith, C.R.; Näslund, L.-Å.; May, S.J.; Hultman, L.;
Gogotsi, Y.; Eklund, P.; et al. Transparent Conductive Two-Dimensional Titanium Carbide Epitaxial Thin
Films. Chem. Mater. 2014, 26, 2374–2381. [CrossRef] [PubMed]
35. Mariano, M.; Mashtalir, O.; Antonio, F.Q.; Ryu, W.-H.; Deng, B.; Xia, F.; Gogotsi, Y.; Taylor, A.D.
Solution-processed titanium carbide MXene films examined as highly transparent conductors. Nanoscale
2016, 8, 16371–16378. [CrossRef] [PubMed]
36. Lai, S.; Jeon, J.; Jang, S.K.; Xu, J.; Choi, Y.J.; Park, J.-H.; Hwang, E.; Lee, S. Surface group modification and
carrier transport properties of layered transition metal carbides (Ti2 CTx , T: –OH, –F and –O). Nanoscale 2015,
7, 19390–19396. [CrossRef] [PubMed]
37. Naguib, M.; Halim, J.; Lu, J.; Cook, K.M.; Hultman, L.; Gogotsi, Y.; Barsoum, M.W. New Two-Dimensional
Niobium and Vanadium Carbides as Promising Materials for Li-Ion Batteries. J. Am. Chem. Soc. 2013,
135, 15966–15969. [CrossRef]
38. Xie, Y.; Dall’Agnese, Y.; Naguib, M.; Gogotsi, Y.; Barsoum, M.W.; Zhuang, H.L.; Kent, P.R.C.
Prediction and Characterization of MXene Nanosheet Anodes for Non-Lithium-Ion Batteries. ACS Nano
2014, 8, 9606–9615. [CrossRef]
39. Shahzad, F.; Alhabeb, M.; Hatter, C.B.; Anasori, B.; Hong, S.M.; Koo, C.M.; Gogotsi, Y.
Electromagnetic interference shielding with 2D transition metal carbides (MXenes). Science 2016,
353, 1137–1140. [CrossRef]
40. Fan, G.; Li, X.; Ma, Y.; Zhang, Y.; Wu, J.; Xu, B.; Sun, T.; Gao, D.-J.; Bi, J. Magnetic, recyclable Pty Co1−y /Ti3 C2 X2
(X = O, F) catalyst: A facile synthesis and enhanced catalytic activity for hydrogen generation from the
hydrolysis of ammonia borane. New J. Chem. 2017, 41, 2793–2799. [CrossRef]
41. Xue, M.; Wang, Z.; Yuan, F.; Zhang, X.; Wei, W.; Tang, H.; Li, C. Preparation of TiO2 /Ti3 C2 Tx hybrid
nanocomposites and their tribological properties as base oil lubricant additives. RSC Adv. 2017,
7, 4312–4319. [CrossRef]
42. Zhang, X.; Xu, J.; Wang, H.; Zhang, J.; Yan, H.; Pan, B.; Zhou, J.; Xie, Y. Ultrathin nanosheets of MAX
phases with enhanced thermal and mechanical properties in polymeric compositions: Ti3 Si0.75 Al0.25 C2 .
Angew. Chem. Int. Ed. 2013, 52, 4361–4365. [CrossRef] [PubMed]
43. Peng, Q.; Guo, J.; Zhang, Q.; Xiang, J.; Liu, B.; Zhou, A.; Liu, R.; Tian, Y. Unique Lead Adsorption Behavior of
Activated Hydroxyl Group in Two-Dimensional Titanium Carbide. J. Am. Chem. Soc. 2014, 136, 4113–4116.
[CrossRef] [PubMed]
44. Guo, J.; Peng, Q.; Fu, H.; Zou, G.; Zhang, Q. Heavy-Metal Adsorption Behavior of Two-Dimensional
Alkalization-Intercalated MXene by First-Principles Calculations. J. Phys. Chem. C 2015,
119, 20923–20930. [CrossRef]
45. Mashtalir, O.; Cook, K.M.; Mochalin, V.; Crowe, M.; Barsoum, M.W.; Gogotsi, Y. Dye adsorption and
decomposition on two-dimensional titanium carbide in aqueous media. J. Mater. Chem. A 2014,
2, 14334–14338. [CrossRef]
46. Liu, F.; Zhou, A.; Chen, J.; Zhang, H.; Cao, J.; Wang, L.; Hu, Q. Preparation and methane adsorption of
two-dimensional carbide Ti2 C. Adsorption 2016, 22, 915–922. [CrossRef]
47. Lin, H.; Wang, X.; Yu, L.; Chen, Y.; Cui, X. Two-Dimensional Ultrathin MXene Ceramic Nanosheets for
Photothermal Conversion. Nano Lett. 2016, 17, 384–391. [CrossRef]
48. Khazaei, M.; Arai, M.; Sasaki, T.; Chung, C.-Y.; Venkataramanan, N.S.; Estili, M.; Sakka, Y.; Kawazoe, Y.
Novel Electronic and Magnetic Properties of Two-Dimensional Transition Metal Carbides and Nitrides.
Adv. Funct. Mater. 2012, 23, 2185–2192. [CrossRef]
Sensors 2020, 20, 5434 17 of 19

49. Khazaei, M.; Ranjbar, A.; Ghorbani-Asl, M.; Arai, M.; Sasaki, T.; Liang, Y.; Yunoki, S. Nearly free electron
states in MXenes. Phys. Rev. B 2016, 93, 205125. [CrossRef]
50. Si, C.; Zhou, J.; Sun, Z. Half-Metallic Ferromagnetism and Surface Functionalization-Induced Metal–Insulator
Transition in Graphene-like Two-Dimensional Cr2C Crystals. ACS Appl. Mater. Interfaces 2015,
7, 17510–17515. [CrossRef]
51. Gao, G.; Ding, G.; Li, J.; Yao, K.; Wu, M.; Qian, M. Monolayer MXenes: Promising half-metals and spin
gapless semiconductors. Nanoscale 2016, 8, 8986–8994. [CrossRef]
52. Berdiyorov, G.R. Optical properties of functionalized Ti3 C2 T2 (T = F, O, OH) MXene: First-principles calculations.
AIP Adv. 2016, 6, 55105. [CrossRef]
53. Zhang, H.; Yang, G.; Zuo, X.; Tang, H.; Yang, Q.; Li, G. Computational studies on the structural, electronic and
optical properties of graphene-like MXenes (M2 CT2 , M = Ti, Zr, Hf; T = O, F, OH) and their potential
applications as visible-light driven photocatalysts. J. Mater. Chem. A 2016, 4, 12913–12920. [CrossRef]
54. Khazaei, M.; Arai, M.; Sasaki, T.; Estili, M.; Sakka, Y. Two-dimensional molybdenum carbides:
Potential thermoelectric materials of the MXene family. Phys. Chem. Chem. Phys. 2014,
16, 7841–7849. [CrossRef] [PubMed]
55. Kim, H.; Anasori, B.; Gogotsi, Y.; Alshareef, H.N. Thermoelectric Properties of Two-Dimensional
Molybdenum-Based MXenes. Chem. Mater. 2017, 29, 6472–6479. [CrossRef]
56. Yu, X.-F.; Li, Y.; Cheng, J.-B.; Liu, Z.-B.; Li, Q.-Z.; Li, W.-Z.; Yang, X.; Xiao, B. Monolayer Ti2 CO2 : A Promising
Candidate for NH3 Sensor or Capturer with High Sensitivity and Selectivity. ACS Appl. Mater. Interfaces
2015, 7, 13707–13713. [CrossRef]
57. Yadav, A.; Dashora, A.; Patel, N.; Miotello, A.; Press, M.; Kothari, D. Study of 2D MXene Cr2 C material for
hydrogen storage using density functional theory. Appl. Surf. Sci. 2016, 389, 88–95. [CrossRef]
58. Hu, Q.; Sun, D.; Wu, Q.; Wang, H.; Wang, L.; Liu, B.; Zhou, A.; He, J. MXene: A New Family of Promising
Hydrogen Storage Medium. J. Phys. Chem. A 2013, 117, 14253–14260. [CrossRef]
59. Lei, J.; Kutana, A.; Yakobson, B.I. Predicting stable phase monolayer Mo2 C (MXene), a superconductor with
chemically-tunable critical temperature. J. Mater. Chem. C 2017, 5, 3438–3444. [CrossRef]
60. Si, C.; Jin, K.-H.; Zhou, J.; Sun, Z.; Liu, F. Large-Gap Quantum Spin Hall State in MXenes: D-Band Topological
Order in a Triangular Lattice. Nano Lett. 2016, 16, 6584–6591. [CrossRef]
61. Liang, Y.; Khazaei, M.; Ranjbar, A.; Arai, M.; Yunoki, S.; Kawazoe, Y.; Weng, H.; Fang, Z. Theoretical prediction
of two-dimensional functionalized MXene nitrides as topological insulators. Phys. Rev. B 2017,
96, 195414. [CrossRef]
62. Kumar, S.; Lei, Y.; Alshareef, N.H.; Quevedo-Lopez, M.; Salama, K.N. Biofunctionalized two-dimensional
Ti3 C2 MXenes for ultrasensitive detection of cancer biomarker. Biosens. Bioelectron. 2018, 121, 243–249.
[CrossRef] [PubMed]
63. Zhou, S.; Gu, C.; Li, Z.; Yang, L.; He, L.; Wang, M.; Huang, X.; Zhou, N.; Zhang, Z. Ti3 C2 Tx MXene
and polyoxometalate nanohybrid embedded with polypyrrole: Ultra-sensitive platform for the detection
of osteopontin. Appl. Surf. Sci. 2019, 498, 143889. [CrossRef]
64. Chia, H.L.; Mayorga-Martinez, C.C.; Antonatos, N.; Sofer, Z.; Gonzalez-Julian, J.J.; Webster, R.D.; Pumera, M.
MXene Titanium Carbide-based Biosensor: Strong Dependence of Exfoliation Method on Performance.
Anal. Chem. 2020, 92, 2452–2459. [CrossRef]
65. Bollella, P.; Katz, E. Enzyme-Based Biosensors: Tackling Electron Transfer Issues. Sensors 2020, 20, 3517.
[CrossRef] [PubMed]
66. Gu, H.; Xing, Y.; Xiong, P.; Tang, H.; Li, C.; Chen, S.; Zeng, R.; Han, K.; Shi, G. Three-Dimensional
Porous Ti3 C2 Tx MXene–Graphene Hybrid Films for Glucose Biosensing. ACS Appl. Nano Mater. 2019,
2, 6537–6545. [CrossRef]
67. Rakhi, R.B.; Nayak, P.; Xia, C.; Alshareef, H.N.; Nayuk, P. Novel amperometric glucose biosensor based on
MXene nanocomposite. Sci. Rep. 2016, 6, 36422. [CrossRef]
68. Koyappayil, A.; Chavan, S.G.; Mohammadniaei, M.; Go, A.; Hwang, S.Y.; Lee, M.-H. β-Hydroxybutyrate
dehydrogenase decorated MXene nanosheets for the amperometric determination of β-hydroxybutyrate.
Microchim. Acta 2020, 187, 277. [CrossRef]
69. Wang, F.; Yang, C.; Duan, M.; Tang, Y.; Zhu, J. TiO2 nanoparticle modified organ-like Ti3 C2 MXene
nanocomposite encapsulating hemoglobin for a mediator-free biosensor with excellent performances.
Biosens. Bioelectron. 2015, 74, 1022–1028. [CrossRef]
Sensors 2020, 20, 5434 18 of 19

70. Liu, H.; Duan, C.; Yang, C.; Shen, W.; Wang, F.; Zhu, Z. A novel nitrite biosensor based on the
direct electrochemistry of hemoglobin immobilized on MXene-Ti3 C2 . Sens. Actuators B Chem. 2015,
218, 60–66. [CrossRef]
71. Ma, B.-K.; Li, M.; Cheong, L.-Z.; Weng, X.-C.; Shen, C.; Huang, Q. Enzyme-MXene Nanosheets: Fabrication and
Application in Electrochemical Detection of H2 O2 . J. Inorg. Mater. 2020, 35, 131–138.
72. Zhou, L.; Zhang, X.; Ma, L.; Gao, J.; Jiang, Y. Acetylcholinesterase/chitosan-transition metal carbides
nanocomposites-based biosensor for the organophosphate pesticides detection. Biochem. Eng. J. 2017,
128, 243–249. [CrossRef]
73. Jiang, Y.; Zhang, X.; Pei, L.; Yue, S.; Ma, L.; Zhou, L.; Huang, Z.; He, Y.; Gao, J. Silver nanoparticles
modified two-dimensional transition metal carbides as nanocarriers to fabricate acetycholinesterase-based
electrochemical biosensor. Chem. Eng. J. 2018, 339, 547–556. [CrossRef]
74. Song, D.; Jiang, X.; Li, Y.; Lu, X.; Luan, S.; Wnag, Y.; Li, Y.; Gao, F. Metal−Organic frameworks-derived
MnO2 /Mn3 O4 microcuboids with hierarchically ordered nanosheets and Ti3 C2 MXene/Au NPs composites
for electrochemical pesticide detection. J. Hazard. Mater. 2019, 373, 367–376. [CrossRef] [PubMed]
75. Wang, G.; Sun, J.; Yao, Y.; An, X.; Zhang, H.; Chu, G.; Jiang, S.; Guo, Y.; Sun, X.; Liu, Y. Detection of Inosine
Monophosphate (IMP) in Meat Using Double-Enzyme Sensor. Food Anal. Methods 2019, 13, 420–432. [CrossRef]
76. Fang, L.; Liao, X.; Jia, B.; Shi, L.; Kang, L.; Zhou, L.; Kong, W. Recent progress in immunosensors for pesticides.
Biosens. Bioelectron. 2020, 164, 112255. [CrossRef]
77. Cheng, N.; Song, Y.; Shi, Q.; Du, D.; Liu, D.; Luo, Y.; Xu, W.; Lin, Y. Au@Pd Nanopopcorn and
Aptamer Nanoflower Assisted Lateral Flow Strip for Thermal Detection of Exosomes. Anal. Chem.
2019, 91, 13986–13993. [CrossRef]
78. Fan, Y.; Shi, S.; Ma, J.; Guo, Y. A paper-based electrochemical immunosensor with reduced graphene
oxide/thionine/gold nanoparticles nanocomposites modification for the detection of cancer antigen 125.
Biosens. Bioelectron. 2019, 135, 1–7. [CrossRef]
79. Cheng, N.; Song, Y.; Zeinhom, M.M.A.; Chang, Y.-C.; Sheng, L.; Li, H.; Du, D.; Li, L.; Zhu, M.-J.; Luo, Y.; et al.
Nanozyme-Mediated Dual Immunoassay Integrated with Smartphone for Use in Simultaneous Detection
of Pathogens. ACS Appl. Mater. Interfaces 2017, 9, 40671–40680. [CrossRef]
80. Cheng, N.; Xu, Y.; Huang, K.; Chen, Y.; Yang, Z.; Luo, Y.; Xu, W. One-step competitive lateral flow biosensor
running on an independent quantification system for smart phones based in-situ detection of trace Hg(II) in
tap water. Food Chem. 2017, 214, 169–175. [CrossRef]
81. Pan, G.; Zhao, G.; Wei, M.; Wang, Y.; Zhao, B. Design of nanogold electrochemical immunosensor for
detection of four phenolic estrogens. Chem. Phys. Lett. 2019, 732, 136657. [CrossRef]
82. Angulo-Ibáñez, A.; Eletxigerra, U.; Lasheras, X.; Campuzano, S.; Merino, S. Electrochemical tropomyosin
allergen immunosensor for complex food matrix analysis. Anal. Chim. Acta 2019, 1079, 94–102.
[CrossRef] [PubMed]
83. Kunene, K.; Weber, M.; Sabela, M.; Voiry, D.; Kanchi, S.; Bisetty, K.; Bechelany, M. Highly-efficient
electrochemical label-free immunosensor for the detection of ochratoxin A in coffee samples. Sens. Actuators
B Chem. 2020, 305, 127438. [CrossRef]
84. Wang, H.; Li, H.; Huang, Y.; Xiong, M.; Wang, F.; Li, C. A label-free electrochemical biosensor for highly
sensitive detection of gliotoxin based on DNA nanostructure/MXene nanocomplexes. Biosens. Bioelectron.
2019, 142, 111531. [CrossRef] [PubMed]
85. Xu, Y.; Wei, Y.; Cheng, N.; Huang, K.; Wang, W.; Zhang, L.; Xu, W.; Luo, Y. Nucleic Acid Biosensor Synthesis
of an All-in-One Universal Blocking Linker Recombinase Polymerase Amplification with a Peptide Nucleic
Acid-Based Lateral Flow Device for Ultrasensitive Detection of Food Pathogens. Anal. Chem. 2017, 90,
708–715. [CrossRef] [PubMed]
86. Chen, J.; Tong, P.; Huang, L.; Yu, Z.; Tang, D. Ti3 C2 MXene nanosheet-based capacitance immunoassay
with tyramine-enzyme repeats to detect prostate-specific antigen on interdigitated micro-comb electrode.
Electrochim. Acta 2019, 319, 375–381. [CrossRef]
87. Khan, R.; Ben Aissa, S.; Sherazi, T.A.; Catanante, G.; Hayat, A.; Marty, J.-L. Development of an Impedimetric
Aptasensor for Label Free Detection of Patulin in Apple Juice. Molecules 2019, 24, 1017. [CrossRef]
88. Zheng, J.; Wang, B.; Ding, A.; Weng, B.; Chen, J. Synthesis of MXene/DNA/Pd/Pt nanocomposite for sensitive
detection of dopamine. J. Electroanal. Chem. 2018, 816, 189–194. [CrossRef]
Sensors 2020, 20, 5434 19 of 19

89. Yan, X.; Gu, Y.; Li, C.; Tang, L.; Zheng, B.; Li, Y.; Zhang, Z.; Yang, M. Synergetic catalysis based on the proline
tailed metalloporphyrin with graphene sheet as efficient mimetic enzyme for ultrasensitive electrochemical
detection of dopamine. Biosens. Bioelectron. 2016, 77, 1032–1038. [CrossRef]
90. Salamon, J.; Sathishkumar, Y.; Ramachandran, K.; Lee, Y.S.; Yoo, D.; Kim, A.R.; Kumar, G.G. One-pot synthesis
of magnetite nanorods/graphene composites and its catalytic activity toward electrochemical detection
of dopamine. Biosens. Bioelectron. 2015, 64, 269–276. [CrossRef]
91. Peng, X.; Zhang, Y.; Lu, D.; Guo, Y.-J.; Guo, S. Ultrathin Ti3 C2 nanosheets based “off-on” fluorescent nanoprobe
for rapid and sensitive detection of HPV infection. Sens. Actuators B Chem. 2019, 286, 222–229. [CrossRef]
92. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018:
GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer
J. Clin. 2018, 68, 394–424. [CrossRef] [PubMed]
93. Khan, R.; Sherazi, T.A.; Catanante, G.; Rasheed, S.; Marty, J.-L.; Hayat, A. Switchable fluorescence sensor
toward PAT via CA-MWCNTs quenched aptamer-tagged carboxyfluorescein. Food Chem. 2020, 312, 126048.
[CrossRef] [PubMed]
94. Zhang, Q.; Wang, F.; Zhang, H.; Zhang, Y.; Liu, M.; Liu, Y. Universal Ti3 C2 MXenes Based Self-Standard
Ratiometric Fluorescence Resonance Energy Transfer Platform for Highly Sensitive Detection of Exosomes.
Anal. Chem. 2018, 90, 12737–12744. [CrossRef] [PubMed]
95. Shi, X.; Wang, H.; Xie, X.; Xue, Q.; Zhang, J.; Kang, S.; Wang, C.; Liang, J.; Chen, Y. Bioinspired Ultrasensitive
and Stretchable MXene-Based Strain Sensor via Nacre-Mimetic Microscale “Brick-and-Mortar” Architecture.
ACS Nano 2018, 13, 649–659. [CrossRef] [PubMed]
96. Song, D.; Li, X.; Li, X.-P.; Jia, X.; Min, P.; Yu, Z.-Z. Hollow-structured MXene-PDMS composites as flexible,
wearable and highly bendable sensors with wide working range. J. Colloid Interface Sci. 2019, 555, 751–758.
[CrossRef] [PubMed]
97. Cheng, Y.; Ma, Y.; Li, L.; Zhu, M.; Yue, Y.; Liu, W.; Wang, L.; Jia, S.; Li, C.; Qi, T.; et al. Bioinspired Microspines
for a High-Performance Spray Ti3 C2 Tx MXene-Based Piezoresistive Sensor. ACS Nano 2020, 14, 2145–2155.
[CrossRef] [PubMed]
98. Guo, Y.; Zhong, M.; Fang, Z.; Wan, P.; Yu, G. A Wearable Transient Pressure Sensor Made
with MXene Nanosheets for Sensitive Broad-Range Human–Machine Interfacing. Nano Lett. 2019,
19, 1143–1150. [CrossRef]
99. Li, H.; Du, Z. Preparation of a Highly Sensitive and Stretchable Strain Sensor of MXene/Silver
Nanocomposite-Based Yarn and Wearable Applications. ACS Appl. Mater. Interfaces 2019,
11, 45930–45938. [CrossRef]
100. Liao, H.; Guo, X.; Wan, P.; Yu, G. Conductive MXene Nanocomposite Organohydrogel for Flexible, Healable,
Low-Temperature Tolerant Strain Sensors. Adv. Funct. Mater. 2019, 29, 1904507. [CrossRef]
101. Chen, Z.; Hu, Y.; Zhuo, H.; Liu, L.; Jing, S.; Zhong, L.; Peng, X.; Sun, R.-C. Compressible, Elastic,
and Pressure-Sensitive Carbon Aerogels Derived from 2D Titanium Carbide Nanosheets and Bacterial
Cellulose for Wearable Sensors. Chem. Mater. 2019, 31, 3301–3312. [CrossRef]
102. Lei, Y.; Zhao, W.; Zhang, Y.-Z.; Jiang, Q.; He, J.; Baeumner, A.J.; Wolfbeis, O.S.; Wang, Z.L.;
Salama, K.N.; Alshareef, H.N. A MXene-Based Wearable Biosensor System for High-Performance In Vitro
Perspiration Analysis. Small 2019, 15, e1901190. [CrossRef] [PubMed]

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