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J. Funct. Biomater. 2022, 13, 27 14 of 36 N-hydroxysuccinimide (PAA-NHS) ester to make biointerface with wet tissue. The bio- functionality of electrodes in vivo was tested by implanting the electrode in the right atrium and apex of a rat heart, by which stable epicardial ECG with high signal to noise ratio was monitored. It was found that after 14 days the ECG signals became stronger, as a proof of successful biointerface integration [73]. Another noninvasive class of biointer- faces are temporary electronic tattoos for integration to human skin. These cheap accessi- ble biointerfaces can be used to monitor human body status such as recording brain, heart and muscle activities. Kireev et al. developed a facile protocol to obtain graphene elec- tronic tattoos using commercially available CVD-grown graphene without the need for trained labor. They found bilayer graphene electronic tattoos show skin impedance in the range of 8–10 kΩ and sheet resistance as low as 1kΩ/sq compared to monolayer graphene, suggesting reproducible performance of bilayer graphene with low enough impedance to allow current injection [74]. Although applications of 2DNMs in bioelectronics were first fueled by the emergence of graphene, recently nongraphene 2D materials (e.g., MXenes) have been investigated extensively in biosensors and wearable technologies due to their functionality and physi- ochemical features that outperform other 2DNMs (i.e., graphene) for biomedical applica- tions. 2D MXenes are conductive thin platforms with high surface area containing chem- ically reactive sites useful for biofunctionalization. These functional groups make the sur- face of MXenes hydrophilic compared to other similar 2DNMs, which allows solution preparation of MXenes in aqueous media. Moreover although high conductivity can also be obtained by other materials such as metal NPs and graphene, there are still drawbacks to their application in wearable biocompatible devices [75]. For instance, toxicity of metal NPs is debatable [75], and they normally need a high temperature annealing process which makes them inappropriate for room temperature polymer-based substrates [76]. Graphene, on the other hand, needs to be obtained by graphene oxide reduction [77], which needs high temperature thermal treatment in the presence of hazardous chemicals, ending up in a less hydrophilic layer not good enough for water-based ink solutions [78]. This is why MXenes, with high conductivity and hydrophilicity, are appropriate alterna- tives for flexible and implantable bioelectronic devices. MXenes have been utilized in fa- cilitating charge transfer between electrode and redox enzymes in the enzymatic biosen- sor technologies due to their superior electrical conductivity. Therefore, they have been good substitutes for other conducting nanomaterials, thanks to their biocompatibility. Black phosphorene (BP) is another class of 2DNMs which can be prepared by exfoli- ating black phosphorus crystal with high charge carrier mobility, which makes it suitable for electronic devices. However, exfoliated BP has intrinsic instability in ambient condi- tions, and is prone to degradation and oxidation in air and water environments [79]. One way to passivate BP against corrosion is to combine it with other conductive stable 2D materials such as MXene. In a study performed by Zhu and co-workers [80], titanium carbide MXene (Ti3C2-MXene) nanohybrid with two-dimensional phosphorene was pre- pared by electrostatic self-assembly. The nanomaterial then was mounted on laser-in- duced porous graphene and used as a nonenzymatic electrode for detection of phytoreg- ulator α-naphthalene acetic acid (NAA) residues in agricultural products through a port- able wireless electrochemical miniworkstation. The sensor revealed a wide linear range of 0.02–40 μM and a low limit of detection (LOD) of 1.6 nM [80]. Antimonene with similar properties to BP also holds much attention for biosensor application [81]. In a study, an- timonene functionalized with supramolecular oligonucleotide and was applied to detect certain DNA sequences and BRCA1 gene mutation caused by breast cancer in real samples [82]. Therefore, this class of 2DNMs with the facile preparation method can potentially be an inexpensive alternative for traditional time-consuming gene assays. Nanostructured topological insulators are narrow bandgap 2D materials with high carrier mobility, catalytic activity and delocalized metallic surface states that allow fast interfacial charge dynamic, which leads to highly sensitive electrochemical sensing plat- forms [83]. Zhao and co-workers synthesized microflakes of Bi2Te3 with a sensitivity ofPDF Image | Nanomaterials beyond Graphene for Biomedical Applications
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