**Abstract**

This chapter provides information about basic properties of MXenes (2D nanomaterials) that are attractive for a design of various types of nanobiosensors. The second part of the chapter discusses MXene synthesis and various protocols for modification of MXene making it a suitable matrix for immobilization of bioreceptors such as antibodies, DNA aptamers or DNA molecules. The final part of the chapter summarizes examples of MXene-based nanobiosensors developed using optical, electrochemical and nanomechanical transducing schemes. Operational characteristics of such devices such as sensitivity, limit of detection, assay time, assay reproducibility and potential for multiplexing are provided. In particular MXene-based nanobiosensors for detection of a number of cancer biomarkers are shown here.

**Keywords:** MXene, nanomaterials, biosensors, cancer, biomarkers

#### **1. Introduction**

#### **1.1 MXenes: their precursors, characterization, unique properties and applications**

Nanomaterials of the 2D kind are in the research spotlight due to their superior properties like ultrathin structure and intriguing physico-chemical properties [1–3]. Graphene has made researchers believing in extracting single layer transition metal dichalcogenides, which in turn has led to extensive research dedicated towards 2D nanomaterials [4, 5]. Since their inception, 2D nanomaterials have been characterized to have exceptional electronic, mechanical, and optical properties. These outstanding characteristics have driven research to use them in almost all fields of materials science and nanotechnology [6–8]. Rather recently in 2011 and 2012, Gogotsi, Barsoum, and colleagues have successfully prepared a new kind of 2D nanomaterial - MXenes, composed of a large group of transition metal carbides and carbonitrides [9–13]. These 2D nanomaterials are found to possess many striking properties and boost attraction in applications such as energy storage [14–16], electromagnetic shielding [17, 18], water treatment [19, 20], disease treatment [21] and (bio)sensing [22, 23], MXenes are made up of atomic layers of different materials like transition metal carbides, nitrides, or carbonitrides. All MAX phases consist of twodimensional slabs of close-packed alternating layers of *M* and *A*, where *M* is a transition metal, *A* is an A-group element and *X* is C and/or N [23].

The selective chemical etching of "A" in "MAX" phases have led to successful synthesis of MXenes. MAX phases are found to have elusive properties like stiff elasticity, good thermal and electrical conductivity, as well as relatively low thermal expansion coefficients and resistance towards chemical attack. There is a general formula for MXene synthesis where, "MAX" phases have a formula of M*n+1*AX*n*, with "M" meaning early d-transition metal, "A" representing the main group spelement, and "X" indicates C and/or N [24]. Hence, with this analogy, more than 70 different kinds of MXenes with different M and X are theoretically possible to synthesize. Out of these theoretical MXene types, 20 different combinations of MXenes have been synthesized successfully [25]. MXenes can conduct heat and electricity like metals and are strong and brittle like ceramics with high surface area. Exfoliated MXene exhibits higher pseudocapacitance than most capacitive materials [26]. Additionally, the MXene-have properties like a clay. Furthermore, Ca2+, Mg2+ and Al3+ ions (intercalated polyvalent cations) have all shown a huge storage power capacity [27–29]. It needs to be stressed out that energy storage capacity, high conductivity, photochemical properties, modulated surface chemistry and tunable composition make MXene and their derivatives very perspective to (bio)sensing applications.

done by a simple shaking or by sonication and prolonged sonication time results in production of MXene with small size of nanosheets and high density of defects [61]. An alternative to use of highly corrosive and harmful HF is to employ small organic molecules or ions such as urea [62], dimethyl sulphoxide (DMSO) [12] (only for Ti3C2Tx MXene) or isopropylamine as etchants [63]. MAX phase containing Si can be also exfoliated using tetrabutylammonium hydroxide (TBAOH) and tetramethy-

*Ti3C2 MXene-Based Nanobiosensors for Detection of Cancer Biomarkers*

Since introduction of nanolayered and machinable MXenes in 2011 by Gogotsi and co-workers through wet-etching process with HF to obtain multilayered flakes of Ti3C2T*<sup>x</sup>* [13], few improvements in MXene synthesis and MXene-nanocomposite preparation resulted in various elemental composition and surface functionality [65]. In last few years the single layers of MXene were isolated adding salts or organic solvents (NH4HF2, tetrabuthylammonium hydroxide, isopropylamine) during synthesis process and resulted in delaminated MXene layers. The significant breakthrough for MXene synthesis named as "clay method" in 2014 was based on *in situ* formation of HF (LiF/HCl). The lattice *c* parameter increased to a value of ≈40 Å by applying LiF-HCl as an etchant to produce Ti3C2T*<sup>x</sup>* instead of HF etchant with a lattice *c* parameter of 20 Å [60]. The battery of techniques were employed to observe variations in the composition of Ti3C2Tx MXene produced either by HF or

scanning electron microscopy (SEM), X-ray diffraction method (XRD), energydispersive X-ray spectroscopy (EDS) techniques [59]. The most suitable combination presented utilization of LiF/HCl as an etchant with minimally intensive layer delamination "MILD" method instead of sonication to produce huge MXene flakes with minimum of defects [66]. Ti3C2Tx MXene has become an attractive subject of

demand to improve stability of MXene flakes with a poor resistance in aerated aqueous suspensions resulting in oxidized form with loss of its activity for potential applications [67]. The optimization of etching process is cardinal to access single- to few-layer Ti3C2 MXene flakes. SEM technique providing information about flake size and distribution revealed formation of aggregates on the surface varying in size i.e. having few μm in size or with size larger than 10 μm in a lateral dimension. It was found out by atomic force microscopy (AFM), that thickness of single MXene monolayer was (1.1 0.1) nm for Ti3C2Tx [68]. Platinum nanoparticles with average diameter of 3 nm were homogeneously distributed on the MXene sheets surface, that was found out by transmission electron microscopy (TEM) [69]. MXene and oxidized MXene were analyzed and differentiated by applying Raman spectroscopy method providing more detailed information about the characteristic vibrational bands and the dependence thickness of Ti3C2Tx layers on Raman signal

The electrochemical behavior employing methods like cyclic voltammetry (CV),

chronoamperometry (CA), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) revealed significant findings related to the electrochemical activity of MXene. The electrochemical investigation of Ti3C2Tx MXene to detect significant analytes (O2, H2O2 and NADH) was performed by applying cyclic voltammetry and chronoamperometry techniques, whereas Ti3C2TX

demonstrated electrocatalytic activity towards H2O2 reduction with LOD at nanomolar level [68]. Unfortunately, formation of TiO2 layer or domains with

H, 13C and 19F NMR),

) in supercapacitors and an excel-

). On the other hand there is still

lammonium hydroxide (TMAOH) [64].

*DOI: http://dx.doi.org/10.5772/intechopen.94309*

LiF-HCl method including nuclear magnetic resonance (<sup>1</sup>

interest due its high capacitance (1500 F cm<sup>3</sup>

lent high metallic conductivity (15,000 S cm<sup>1</sup>

enhancement [68–71].

**221**

**3. MXene characterization**

2D MXenes are candidates for energy storage [30] (Li-ion batteries, supercapacitors) and electromagnetic interference shielding applications [31–35] and in the form of composites become ever more useful for sensing as *e.g*. gas sensing devices [36, 37], pressure sensor [38, 39] and sensors for various analytes [40–43]. Number of other biomedical applications (such as biosensor, biological imaging, photothermal therapy, drug delivery, theranostic nanoplatforms and antibacterial agents) have become a challenge for MXenes [44]. The antibacterial properties making them potentially appealing for nanomedicine were proved for (Ti3C2Tx) MXene quantum dots [45], MXene-hybridized silane film [46], Cu2O/ MXene [47] and MXene-gold nanoclusters [48] *etc*. The multifunctional MXenes have attracted attention in biosensing [49, 50] with the aim at the ultrasensitive determination of cancer diseases related biomarkers. Examples include biosensors based on Ti3C2 MXenes-Au NPs hybrids, delaminated Ti3C2Tx MXene@AuNPs, nanohybrid of Ti3C2Tx MXene and phosphomolybdic acid (PMo12) embedded with polypyrrole, MXene-TiO2/BiVO4 hybrid and AuNPs/Ti3C2 MXene threedimensional nanocomposite for detection of carcinoembryonic antigen [51], prostate specific antigen [52], osteopontin [53], CD44 [54] and microRNA-155 [55], respectively.

#### **2. MXene synthesis**

Generally, top-down selective etching process is used for the synthesis of MXenes [56]. Strong etching solutions containing a fluoride ion (F) such as hydrofluoric acid (HF), ammonium difluoride (NH4HF2), and a mixture of hydrochloric acid (HCl) and lithium fluoride (LiF) are used for production of MXene in such processes [57]. Since typically, the etching process results in replacement of the M-A bond by M-O, M-OH, M-H, and M-F bonds on the surface of MXenes, the structure of MXenes can be expressed as M*<sup>n</sup>* + 1X*n*T*<sup>x</sup>* or M*<sup>n</sup>* + 1X*<sup>n</sup>* (M and X are in same form as the MAX phase and T is =O, -OH, -H, or -F) [58, 59].

A single and/or few layers of MXene can be synthetized by exfoliation or delamination of a multilayer structure of a MAX phase. The composition and electrochemical properties of MXene strongly depend on the conditions used during etching procedure [60]. As an example, application of LiF/HCl as etchant led to production of MXene with interlayers intercalated with Li<sup>+</sup> ions. Exfoliation can be *Ti3C2 MXene-Based Nanobiosensors for Detection of Cancer Biomarkers DOI: http://dx.doi.org/10.5772/intechopen.94309*

done by a simple shaking or by sonication and prolonged sonication time results in production of MXene with small size of nanosheets and high density of defects [61]. An alternative to use of highly corrosive and harmful HF is to employ small organic molecules or ions such as urea [62], dimethyl sulphoxide (DMSO) [12] (only for Ti3C2Tx MXene) or isopropylamine as etchants [63]. MAX phase containing Si can be also exfoliated using tetrabutylammonium hydroxide (TBAOH) and tetramethylammonium hydroxide (TMAOH) [64].
