**5. Advanced 2D MXenes-based nanobiosensors as ultrasensitive detection tools**

The link between progressive detection and daily/routine tests is fostered by (bio)sensing platforms employing nanomaterials/nanostructures with outstanding electronic, electrocatalytic, magnetic, mechanical, and optical properties. Novel multifunctional nanometer-sized structures combine advantageous large surface-to-volume ratio, controlled morphology and structure that would allow immobilizing bioreceptors with preserved biocompatibility, biostability and biodistribution [103]. Compared to other 2D materials (graphene, graphitic carbon nitride, MoS2), MXenes nanomaterials carry a unique combination of excellent electrical conductivity, complete metal atomic layers, ease of functionalization, high stability, hydrophilicity, large surface area, ultrathin 2D sheet-like morphology, excellent mechanical properties and good bio-compatibility [49, 77].

*A typical biosensor consists of:*

*5. an interface to the human operator.*

*such an interface;*

**biomarkers detection**

monitoring of clinical response to an intervention.

*pharmacologic responses to a therapeutic intervention.*

**227**

*1. a bioreceptor that specifically bind to the analyte;*

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

*2. an interface architecture where a specific biological event takes place and gives rise to a signal screened by*

The morphology of ultrathin 2D Ti3C2 MXene single or few layered nanosheets with high density of functional groups offers improved biomolecule loading and rapid access to the analyte. The covalent immobilization of biorecognition elements (DNAs, enzymes, proteins, *etc.*) leads not only to improved uniformity and acces-

Jastrzębska *et al*. observed that 2D Ti3C2 MXene superficially oxidized into titanium (III) oxide i.e., Ti2O3 by sonication of MXene flakes followed by a mild thermal oxidation in water at 60°C for 24 h resulted in "fine-tuning" of the toxicity of the flakes to cancerous cell lines. The authors found out, that thermally oxidized samples showed the highest cytotoxic effect, moreover they were selectively toxic towards all cancerous cell

*3. a transducer element converting a biorecognition event into a measurable signal; 4. a computer software able to further process and store measured signal;*

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

sibility of immobilized bioreceptors, but also to higher density of bound bioreceptors, all resulting in an enhanced biosensor performance.

lines with increasing concentration of nanomaterial up to 375 mg L<sup>1</sup> [106].

**5.1 State-of-the-art approaches of MXenes-based nanobiosensors for cancer**

Cancer is one of the deadliest diseases worldwide, and acquiring cancer-specific data by quantitative analysis of cancer-associated biomarkers is crucial to monitor cancer progression and for the early treatment [107]. As reported by the World Health Organization, the year of 2030 should be marked by approximately 12 million cancer related deaths, making cancer a major public health problem and one of the most prominent death-causing factors worldwide. The number of new cases of cancer (cancer incidence) is presently around 439 *per* 100,000 *per* capita *per* year [108]. Early-stage diagnostics of various types of cancer diseases is important since it offers opportunities to extend life expectation of patients. Tumor markers exist in tumor cells themselves or are secreted by tumor cells. In either case the presence of these tumor markers above a set threshold may suggest the existence and/or growth of a tumor. The phrase "tumor marker" is often transposed for the term "biomarker" [109] and *vice versa*. Biomarkers can be applied as an early diagnostic tool, to monitor disease progression, as a prognostic tool and as means for prediction and

*According to the National Institute of Health, a biological marker (biomarker): is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or*

A tumor/cancer marker is a substance produced by a tumor or by the host in response to a cancer cell that can be objectively measured and evaluated as an indicator of cancerous processes within the body. The term tumor marker was firstly coined in 1847 and presently there are more than 100 known different tumor markers [110]. Biomarkers have a great potential for screening and diagnostics because they are present in blood and provide information about the health condition [111]. In healthy individuals, the tumor marker concentration is comparatively

Bioreceptor's intrinsic characteristics including its affinity towards the analyte, structural stability during biosensor's operation and a methodology deployed for bioreceptor immobilization onto the transducing surface can significantly affect sensitivity, selectivity and robustness (reproducibility, stability *etc*.) of a biosensor. The biorecognition element is usually grafted onto a surface, *i.e*., in the close vicinity of the transducer. Additional specifications, which need to be optimized for advanced biosensing performance, are the accessibility of the analyte to the biorecognition site of the bioreceptor, the distance between the bioreceptor and the transducer (surface) and bioreceptor's interfacial density.

Both enhanced biocompatibility and increase of the transducing surface area of the (bio)sensors related to enhanced catalytic activity drive a design of 2D MXene nanomaterial-based biosensors utilizing aptamers, antibodies, enzymes and protein molecules [23, 60, 68]. Ultrathin 2D sheet-like morphology with potential for high density incorporation of a number of functional groups as well as excellent ion intercalation behavior also show up as promising features for (bio)sensing applications [104]. On the other hand the implementation of MXenes as next-generation detection devices will require a substantial improvement of the stability of MXenes towards oxidation.

"Detect-to-protect" biosensors are compact analytical devices converting the biochemical reaction into an analytical and measureable signal. Due to their high specificity which is directly dependent on the receptor used (biomolecules or synthetic compounds), their sensitivity, compact size and simple operation, biosensors are the tool of choice for detection of chemical and biological components. Principally, biosensors are formed by two components, a biorecognition part consisting of a biological or synthetic receptor (enzymes, antibodies, nucleic acids, organelles, plant and animal tissue, whole organism, or organs) that utilizes a specific biochemical or chemical reaction mechanism with an analyte and a transducer where the interaction between a bioreceptor and an analyte is transformed into a measurable signal. There are two major obstacles in biosensor development; incorporation/ immobilization of (bio)receptors in suitable matrix and monitoring/quantifying the interactions between the analytes and these receptors [105].

In order to allow for a rapid screening of analytes/antigens from human samples a real-time analysis is the preferred approach. The corresponding biosensor should be cheap, small, portable and user-friendly.

The key part of a biosensor is the transducer, which screens a physical change accompanying the bioaffinity reaction (*amperometric biosensors, calorimetric biosensors, optical biosensors, piezo-electric biosensors, potentiometric biosensors*).

*A typical biosensor consists of:*

**5. Advanced 2D MXenes-based nanobiosensors as ultrasensitive**

The link between progressive detection and daily/routine tests is fostered by (bio)sensing platforms employing nanomaterials/nanostructures with outstanding electronic, electrocatalytic, magnetic, mechanical, and optical properties. Novel multifunctional nanometer-sized structures combine advantageous large surface-to-volume ratio, controlled morphology and structure that would allow immobilizing bioreceptors with preserved biocompatibility,

biostability and biodistribution [103]. Compared to other 2D materials (graphene, graphitic carbon nitride, MoS2), MXenes nanomaterials carry a unique combination

Bioreceptor's intrinsic characteristics including its affinity towards the analyte, structural stability during biosensor's operation and a methodology deployed for bioreceptor immobilization onto the transducing surface can significantly affect sensitivity, selectivity and robustness (reproducibility, stability *etc*.) of a biosensor. The biorecognition element is usually grafted onto a surface, *i.e*., in the close vicinity of the transducer. Additional specifications, which need to be optimized for

of excellent electrical conductivity, complete metal atomic layers, ease of functionalization, high stability, hydrophilicity, large surface area, ultrathin 2D sheet-like morphology, excellent mechanical properties and good bio-compatibility

advanced biosensing performance, are the accessibility of the analyte to the

"Detect-to-protect" biosensors are compact analytical devices converting the biochemical reaction into an analytical and measureable signal. Due to their high specificity which is directly dependent on the receptor used (biomolecules or synthetic compounds), their sensitivity, compact size and simple operation, biosensors are the tool of choice for detection of chemical and biological components.

Principally, biosensors are formed by two components, a biorecognition part consisting of a biological or synthetic receptor (enzymes, antibodies, nucleic acids, organelles, plant and animal tissue, whole organism, or organs) that utilizes a specific biochemical or chemical reaction mechanism with an analyte and a transducer where the interaction between a bioreceptor and an analyte is transformed into a measurable signal. There are two major obstacles in biosensor development; incorporation/ immobilization of (bio)receptors in suitable matrix and monitoring/quantifying the

In order to allow for a rapid screening of analytes/antigens from human samples a real-time analysis is the preferred approach. The corresponding biosensor should

The key part of a biosensor is the transducer, which screens a physical change accompanying the bioaffinity reaction (*amperometric biosensors, calorimetric biosen-*

*sors, optical biosensors, piezo-electric biosensors, potentiometric biosensors*).

interactions between the analytes and these receptors [105].

be cheap, small, portable and user-friendly.

transducer (surface) and bioreceptor's interfacial density.

biorecognition site of the bioreceptor, the distance between the bioreceptor and the

Both enhanced biocompatibility and increase of the transducing surface area of the (bio)sensors related to enhanced catalytic activity drive a design of 2D MXene nanomaterial-based biosensors utilizing aptamers, antibodies, enzymes and protein molecules [23, 60, 68]. Ultrathin 2D sheet-like morphology with potential for high density incorporation of a number of functional groups as well as excellent ion intercalation behavior also show up as promising features for (bio)sensing applications [104]. On the other hand the implementation of MXenes as next-generation detection devices will require a substantial improvement of the stability of MXenes

**detection tools**

*Novel Nanomaterials*

[49, 77].

towards oxidation.

**226**


The morphology of ultrathin 2D Ti3C2 MXene single or few layered nanosheets with high density of functional groups offers improved biomolecule loading and rapid access to the analyte. The covalent immobilization of biorecognition elements (DNAs, enzymes, proteins, *etc.*) leads not only to improved uniformity and accessibility of immobilized bioreceptors, but also to higher density of bound bioreceptors, all resulting in an enhanced biosensor performance.

Jastrzębska *et al*. observed that 2D Ti3C2 MXene superficially oxidized into titanium (III) oxide i.e., Ti2O3 by sonication of MXene flakes followed by a mild thermal oxidation in water at 60°C for 24 h resulted in "fine-tuning" of the toxicity of the flakes to cancerous cell lines. The authors found out, that thermally oxidized samples showed the highest cytotoxic effect, moreover they were selectively toxic towards all cancerous cell lines with increasing concentration of nanomaterial up to 375 mg L<sup>1</sup> [106].
