MoS₂-based nanostructures: synthesis and applications in medicine

Molybdenum is a transition metal with a partially filled d shell, which predetermines their high chemical activity and ability to form a rich diversity of compounds. Even as pure elements, transition metals exhibit high catalytic activity; this activity could be significantly enhanced by combining them with elements of the oxygen family, such as oxygen and sulphur (figure 2). Among these two-element compounds, molybdenum disulphides attract particular interest due to high chemical activity of sulphur, as well as bioactivity when applied to biological tissues and other biological system due to the role sulphur plays in the formation and activity of iron–sulphur proteins and many important polyatomic molecules. The disulphides feature strong S–S bonds, thus making the metal-disulphide compounds and nano-composites very attractive for numerous mechanical, electrical and other applications [44]. Usually, catalysis using transition metal-based compounds and nanocomposites proceeds by the formation of temporary bonds with the surface of the catalyst, thus weakening the internal bonds in the reactants and promoting desirable chemical reactions. Fundamentally similar mechanisms are involved in the biological catalytic processes.

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Many innovative methods for the fabrication of metal-disulphide materials and molybdenum disulphide (MoS₂) in particular have recently been proposed [45, 46] for a variety of advanced and emerging applications [47, 48]. Indeed, the fabrication approach is known to directly influence the properties, structure and therefore potential applications of MoS₂ nanostructures, eventually resulting in the synthesising of many various types of nanosystems, including nanotubes, fullerenes and encapsulated hollow nanoparticles [43].

• Molybdenum disulphide features an attractive set of material properties for a wide range of applications

The structural configuration of thin singly layered MoS₂ nanoclusters have remained as a critical area of interest to many, as indicated in numerous notable research articles published on that matter [49–51]. The electronic structure of the edge states has direct influence on the chemical properties of these edges. In particular, their reactivity towards hydrogen is facilitated by the ability of hydrogen to form stable chemical bonds with both low-Miller indexed edges of MoS₂. It has been demonstrated that the edges of the nanoclusters are associated with 1D metallic edge states and the triangles can thus be regarded as closed, nanometer-sized wires. In general, it is anticipated that these 1D, metallic edge states will also pertain to other geometries. Having, for instance, a Mo edge with adsorbed S dimers, the step edge will be metallic in nature, having two localized, 1D conducting channels [52]. As illustrated in figure 3((I)(a)), determination of which termination edge is more stable is not trivial owing to the fact that edges may not be simple termination points of stoichiometric MoS₂ under certain sulfiding conditions employed [51].

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The results from numerical simulations employing density functional theory (DFT) calculations have indicated that Mo terminated edge structures exhibit either one figure 3((I)(b)) or two figure 3((I)(c)) S atoms at each edge where a Mo atom is present at the edge. In both of these instances, the Mo atoms are saturated through coordination to six other S atoms (as is the case for Mo atoms in bulk MoS₂). Therefore these two structures exhibit relatively similar stabilities. However, results from DFT simulations have identified that only structures with singular S atoms for each Mo atom at an edge figure 3((I)(d)), result in S atoms at the edges being shifted by half a lattice constant relative to S atoms in the basal plane (as observed through experimental STM imaging). None of the simulated structures (for S terminated edges) appear to be reconstructable, and this is verified with results from STM measurements. Through correlation of calculations with experiment, it can therefore be concluded that the model as illustrated in figure 3((I)(e)) is in good agreement with the structure observed.

Atomically thin S–Mo–S layers contain mostly covalent bonds. On the other hand, the layers in crystalline MoS₂ are held together by much weaker van der Waals forces, figure 3(II), which enable the production of MoS₂ materials with different stacking sequences and thus indifferent polytypisms [53]. It is therefore possible to produce high quality nanostructured MoS₂ films on wafers at the scale needed for industrial applications, with good control over film thickness and uniformity of structure and composition, and excellent quality of crystal [54]. Figures 3(III) and (IV) shows an example of the experimental furnace-based setup used for synthesis of MoS₂ thin films, and correspondence between the surface density of MoO₃ vapour and the size and morphology of MoS₂ films.

Novel ways to engineer and tailor the electronic properties of these systems in order to obtain direct band gap 3D layered nanoparticles, or Mo doped nanowires can then be proposed from numerical calculations. It has been previously shown that single layered MoS₂ nanoparticles do not exhibit significant effects resulting from quantum confinement (even for particles up to ~3.4 nm). The electronic structure in this case is found to be populated dominantly by surface states near the Fermi level. Additionally, a strong dependence of electronic properties on stacking and distance was observed in 3D nanoparticles. Therefore a fusion of these two independent material characteristics was suggested, resulting in MoS₂ nanowires with Mo atoms intercalated within MoS₂ planes to give rise to metallic-like conducting electronic properties [55].

MoS₂ also exhibits very prominent and unique electronic properties, most notably under local deformation as indicated in experiments studying property dependence under the influence of indentation. It was shown that punctual loads only have a negligible effect on quantum transport, thereby substantiating the stable electronic properties of MoS₂ under deformation and mechanical loading. This suggests that MoS₂ monolayers may serve as viable materials for applications in various versatile flexible or wearable electronic devices. MoS₂ also displays numerous highly distinguishable nanostructure morphologies. Some of these nano-organizations include quasi-infinite monolayers, nanonflakes, nanotubes, fullerene-like structures, and other related aggregates and clusters of various sizes and magnitudes in dimension. The array of obtainable structures can be easily obtained through precise tailoring of experimental parameters, with special attention paid to the formation energies of several prototypical species based on MoS_s building blocks as shown in figure 3(V). Evidently, MoS₂ based fullerenes feature sulfur-terminated corners, which have been widely agreed to serve as sites where catalytic activity is understood to originate from. However, figure 3(V) illustrates the unstable nature of fullerene-like quasi 0D nanostructures, which can be attributed to the extent of edge-induced decomposition effects, as seen in room temperature molecular-dynamics simulations. At the other end of the spectrum, the formation energies of triangular shaped nanoflakes are located almost on top of the reference level. This is expected since they are largely similar in nature to complete MoS₂ monolayers which feature edges which are terminated with sulphur. As stated previously, these edges are of interest to many groups working on exploiting unique material phenomena, since they give rise to observed peculiar optical phenomena, as well as account for desirable catalytic activity at these sites [59].

Added focus should be given to quantifying and describing the dependence of optical properties on nanoflake size which can be utilized for applications in biosensing [62] as shown in figure 3(VI). The electronic properties show non-uniformity across the entire nanostructure. As reported, the discrepancies lie in the observation of metallic behaviour at the exterior regions at the flake edges, whereas the interior is observed to possess semiconducting properties. These contrasting location dependent bi-electronic properties indicate a hybrid coexistence of both metallic and semiconducting properties that exist in tandem. Additionally, it is worth noting that the optical absorption spectra in the visible spectrum show distinct red-shifts with the increase of length in the flake edges. This is a clear indication of quantum confinement effects governing the evolution of the materials optical properties at the nanoscale [60].

The results of further investigation on the mechano-structural properties of MoS₂ in a graphene-like honeycomb monolayer (g-MoS₂) configuration under varied loads using DFT are illustrated in figure 3(VII). It was reported that g-MoS₂ has an distinct ability to withstand extensively large strains indicating notable mechanical stability. In these simulations, the ultimate strains for armchair, zigzag and biaxial deformations are given as 0.24, 0.37 and 0.26, respectively. The in-plane stiffness is reported to be as high as 120 N m⁻¹ which is an equivalent of 184 GPa. Given these highly-desirable mechanical properties which include the high tolerable ultimate strains and in-plane stiffness, g-MoS₂ has promise as a material for application in devices for clean energy storage of elastic energy. This interest is also driven by the fact that g-MoS₂ possesses a theoretical energy storage capacity of up to 1.7 MJ kg⁻¹, which is greater than that of typical Li-ion batteries with the added benefits of the former being more environmentally friendly [61]. Finally, it is also worth mentioning that the hexagonal phase of MoS₂ is thermally stable up to temperatures in the excess of 500 °C, presenting a significant advantage for a number of real-life applications [63].

To study the evolution of MoS₂ during the synthesis process, most notably from the nucleation to growth phase in the thermal process, experiments involving the growth of multicrystalline MoS₂ monolayers on SiO₂ with tailored grain sizes were conducted [64]. It was demonstrated that SiO₂ substrates—often utilized as typical substrates in semiconductor technology—could be used for the continuous growth of uniform, homogeneous and high-quality monolayer MoS₂. The growth of MoS₂ on these substrates bears close resemblance to a typical 2D growth model [65], namely one that follows nucleation, growth, and coalescence in chronological order. With the prolonged and continuous growth processes occurring, the nucleation of the grains cause the formation of larger grains, and a homogeneous film is ultimately formed through the process of coalescence. It is observed that monolayer MoS₂ is dominantly observed in most cases, with rare instances of bi- or multilayer MoS₂ observed. Finally, the observation of early growth nucleation with it ceasing at later stages as indicated by the uniform size of larger grains can be explained from a thermodynamics perspective.

The influence of the nature of added precursors on the growth of mono- and multilayer MoS₂, and their resulting morphologies was investigated [66]. It was reported that the choice of precursors—MoO₃ and MoCl₅ in this instance—results in dramatic changes in the resulting morphologies of fabricated MoS₂. Explicitly, an MoO₃ source was reported to give rise to a triangular shaped MoS₂ monolayer, whereas MoCl₅ precursors resulted in fabrication of uniform MoS₂ with an omitted triangular geometry. It is worth noting that in this study, the MoS₂ monolayers were grown on 300 nm Si/SiO₂ substrates. It is therefore postulated that the reaction pathway involving MoCl₅ in excess S may be a single step process. While no clear agreement on the definite reaction pathways have been reached, a possible chemical process is suggested as:

$$\begin{align} \newcommand{\e}{{\rm e}} \displaystyle {\rm MoC}{{{\rm l}}_{5}}+2{\rm S}\to {\rm Mo}{{{\rm S}}_{2}}+5{\rm Cl}{\rm .}\nonumber \end{align} \tag{ 1 }$$

CVD is one of the fundamental methods for material fabrication and is widely used for the synthesis of various MoS₂ nanostructures. However, a diverse set of control parameters intrinsic to CVD technology makes this method sufficiently powerful and flexible to enable fabrication of MoS₂ nanostructures with highly controllable structure and properties.

One of the more successful examples is a method of synthesis of large area (2 cm  ×  2 cm) MoS₂ ultrathin nanofilms through direct sulfurization of annealed Mo foils with a view of their application in solar cells. Given its unique band structure, the MoS₂ layer primarily serves not just as an effective carrier transport layer, but also as a 'blocking layer' during diffusion processes of photo-generated carriers (holes). Through optimization of the structural properties of the MoS₂ nanofilms, a significant increase in photovoltaic response was measured to reach 11.2% in terms of efficiencies for graphene/MoS₂/n-Si Shottky junction-based solar cells. A detailed schematic illustration of the device fabrication process is illustrated in figure 7 [82].

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Lee et al described the synthesis of large-area MoS₂ atomic layers with CVD [83]. Such CVD processes can be implemented to directly synthesize MoS₂ layers on SiO₂/Si substrates with MoO₃ and S powder serving as reactants. It is worth mentioning that substrate treatment prior to growth process has a significant impact on the growth of MoS₂ and should be addressed appropriately for growth of high quality MoS₂. Utilization of graphene-like molecules such as perylene-3,4,9,10-tetracarboxylic acid tetrapotassium salt (PTAS), perylene-3,4,9,10-tetracarboxylic dianhydride and reduced graphene oxide during substrate pre-treatment had been proposed to promote efficient and high quality layer by layer growth of MoS₂. In the experiments performed by Lee et al, MoO₃ powder was placed in ceramic boats and the SiO₂/Si substrate was inverted and mounted on top of the boat.

Cao et al studied the evolution of morphology in monolayer MoS₂ under different chemical environment in a CVD process [84]. In the series of experiments carried out by the group, monolayer MoS₂ nanoflakes were fabricated in a single-step CVD method with solid MoO₃ and S as precursors. A dual temperature zoned annealing furnace was used to provide rapid and accurate temperature control of the two precursors independently. An alumina boat containing solid MoO₃ was placed in the high-temperature zone, whereas the other boat containing solid S powder was placed upstream in the low-temperature zone. The authors report the transformation of the morphologies of the monolayer MoS₂ nanoflakes from a truncated triangular shape, to regular triangular shapes upon increment of the stoichiometric ratio of S:Mo in the process. As a consequence, they are able to precisely tune the optical properties of the MoS₂ flakes. These finding point at good potential for engineering the morphology and optoelectronic properties on monolayer MoS₂ simply through adjusting chemical environments and reactant quantities during the CVD process.

Ling et al studied the role of the seeding promoter in MoS₂ growth by use of CVD [85]. Using various aromatic ring based molecules to promote seeding, highly crystalline and homogeneous MoS₂ monolayers were obtained over large areas through CVD at comparatively low processing temperatures of around 650 °C. Significant dependence of growth quality on seed concentration as well as the effect of different seeding promoters on growth was shown. It was also suggested that it may be possible to derive conditions for optimized concentration of seed molecules to aid and enhance nucleation of MoS₂. Additionally, through studies involving the effect of the nature of the seeding molecule in the facilitation of MoS₂ growth, it was found that PTAS as seeding promoters will result in the ability to fabricate high quality MoS₂ monolayers at low temperatures homogeneously over large areas. Otherwise, MoS₂ particles may still be obtained, however the uniformity of the resulting material in the process may be lost using similar low temperature growth conditions without any seeding promoters.

MoS₂/C nanocomposites that feature multilayered sandwich-like structures based on MoS₂ and C layers were also reported to be successfully synthesized through a synchronized single-step process involving tandem carbonization and sulfurization [86]. Figure 8 illustrates the fabricated MoO₃ and MoS₂/C nanocomposites, accordingly. In this reported tandem single-step process, an intercalation method was employed to prepare the nanocomposites. A mixture of MoO₃, anhydrous ethanol and dodecylamine (DDA) was heated, washed with anhydrous ethanol and then dried after filtration to eventually obtain the MoO₃/DDA powdered composites.

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Özden et al described the CVD growth of monolayer MoS₂ with the main interest to present an overview on the role of growth zone configuration and precursor ratio on the resulting process [87]. The authors again note the difficulty of obtaining monolayer 2D material growth over large areas for extended usage, coherent with the challenges faced by other authors. In this study the authors implemented different substrate holders for the growth of monolayers of Mo and S. Not surprisingly, it was reported that the vapour ratio supplied to the growth zones play a critical role in influencing the shape, size, morphology and uniformity of the resulting MoS₂ nanostructures. This was confirmed through experimental processing with modulated precursor ratios. Two growth approaches, namely horizontal growth, and face down growth, were investigated under identical controlled growth conditions, whereby S:MoO₃ precursor ratio, substrate temperature and pressure conditions were varied in independent series of experiments. Under horizontal growth conditions, it was reported that even though the entire surface was covered with MoS₂ monolayer formations, the grown structures were either found to be too small at the central region of the substrate, or they were located in larger densities at the edges of the substrate compared to that in the central region. In contrast, face down growth gave rise to nanoflakes of larger sizes, and films which are homogeneous over larger areas. These results suggest that the local Mo and S vapour concentrations in CVD growth zones have particularly significant influence on morphology as well as size and uniformity of resulting MoS₂ nanoflakes and grown films [87].

Thermal vapour sulphurization for the growth of large area, continuous MoS₂ atomic layers via vapour-phase mechanism was demonstrated [88]. Firstly the authors utilized a sputtering process in a magnetron sputtering chamber (with Ar/O₂ as the working gases in the chamber) for the deposition of thin Mo and MoO₃ films on c-plane sapphire and SiO₂/Si (0 0 1) substrates. The Ar/O₂ ratios were controlled through mass flow controllers. The starting material underwent a thermal vapour sulphurization process in a tube furnace under N₂ atmosphere at temperatures under 1000 °C for 20–40 min. A SiO₂/bell-shaped MoS₂/SiO₂ sandwich structure on Si was obtained through Mo based sulphurization of the SiO₂/Si (0 0 1) substrates. It is worth noting that Mo sulphurizations that took place on c-plane sapphire substrates under identical conditions have led to the fabrication of the desired MoS₂ atomic layers. The coalescence and ability to control the orientation of the MoS₂ grains in a singular direction throughout the wafer may then be proposed to promote applications of these MoS₂ layers in other practical devices.

A dual step back-to-back exfoliation/restacking process was conducted to study the possibility to expand the interlayer distance in MoS₂ materials to enable their application in energy storage devices as given in figure 9 [89]. In this work, the authors report an electrochemical process that resulted in the intercalation of Li atoms into MoS₂. It is interesting to note the ability to tune the interlayer spacing through the modulation of the number of Li ions inserted between the layers. Expansion of the interlayer spacing results in the weakening of the van der Waals forces between the monolayers of MoS₂, eventually giving rise to the ability to exfoliate monolayered MoS₂ through sonication methods. The sonication then results in MoS₂ monolayers which may restack into layered structures owing to the large basal areas. In the event that foreign species are present during the restacking process, these species may then be interwoven and trapped in the gaps of the restacked MoS₂ monolayers that form interlayer-expanded (IE) MoS₂ as shown in figure 9(b).

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Large-area deposition of MoS₂ by pulsed laser deposition was recently reported [90]. In this work, the authors report a large-area scalable process for the deposition of stoichiometric MoS₂ with up to ten layers. In this reported work, the authors utilized PLD to deposit MoS₂ layers on various substrates, including amorphous, multicrystalline and single crystal substrates. The authors investigated PLD conditions to enable layered deposition of MoS₂ including the cooling rate of the processed substrates, the laser fluency, as well as the deposition pressure. It was found that a precise strategic combination of target composition and PLD conditions resulted in high quality deposition of MoS₂ films on extra-large substrates of up to 50 mm. A notable advantage of such a processing method is the ability to precisely tune the thicknesses of the deposited MoS₂ films uniformly across the entire substrate through variation of the PLD process parameters.

A method for growth of MoS₂ nanosheets [91] within a mesoporous silica shell was developed with a view of applying the resultant materials in H₂S decomposition [92]. In this work, illustrated in figure 10, a synthesis path for MoS₂ nanosheets captured in mesoporous silica was employed. Owing to the fact that MoS₂ may be physically confined in the central cavity of the mesoporous silica material, the MoS₂ then becomes highly curved with an increased density of chemically active Mo sites. The silica shell promotes the thermal stability of MoS₂ and prevents detrimental effects stemming from agglomerate formation. Therefore, the resultant material takes advantage of both catalytic potential of MoS₂ active sites at the edges as well as long term stability properties of traditional catalysts. What results is a solvothermal process that effectively fabricates a nanocatalyst comprising of MoS₂ in a silica mesoporous encapsulant layer. The encapsulated MoS₂ nanosheets are typically observed to be short, with highly curved morphology that results in lower crystallinity and higher strain and defect density [93]. These encapsulated MoS₂ sheets feature extraordinarily high catalytic performance suitable for H₂S decomposition reactions as compared to MoS₂ in the bulk state. Additionally, it was also shown that the encapsulation of the MoS₂ nanosheets in silica enhances stability and performance of the nanocatalyst with a reported 54.7% conversion recorded for up to 38 h.

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A simple, single-step method was used to generate ultra-small MoS₂ nanodots. The method relied on solvothermal decomposition of ammonium tetrathiomolybdate. After they have been modified by glutathione (GSH), thus-generated MoS₂-GSH nanodots displayed very low level of agglomeration in a broad range of physiological buffers, despite their sub-10 nm hydrodynamic diameter. With limited in vitro toxicity and excellent near-infrared absorbance, such nanodots can be used to generate highly-desirable photothermal ablation of cancer cells, see figure 11 [94].

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The process of fabrication of field-emitting transistors based on MoS₂ application was reviewed by Yu et al [95]. The device fabrication process first begins with a thorough cleaning of the target SiO₂/Si substrate using nanostrip and HCl as shown in figure 12. The gate is then formed with a cascading stack of Cr, Au and Pd with dimensions of 5 nm, 30 nm and 30 nm accordingly. Following this, gate patterning is performed through a typical photolithography process. The metal stacks for the gate are strategically chosen to give rise to the best combination of properties which include considerations for adhesion, electrical conductivity as well as work functions. An Al₂O₃ layer that serves as the gate dielectric is then deposited via atomic layer deposition (ALD). The circuit layout then dictates patterning of VIA holes, and the stack is then etched through a reactive ion etch process. Contact pads from Ti/Au stacks are then deposited before the commencement of the MoS₂ transfer process.

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The MoS₂ samples grown through CVD are then coated with poly(methyl methacrylate) (PMMA) to serve as a supporting layer before they are immersed in dilute HF acid. The SiO₂ layer beneath the MoS₂ layer is etched away and the MoS₂/PMMA stack is transferred to the target substrate. Finally, ohmic contacts are made with the deposition of a 90 nm Au layer. Another example of the lithographic process can be used for producing surface-bonded arrays of MoS₂ nanoparticles and ultra-thin structures for specific bio-medical applications, e.g. for biosensors suitable for express-analysis and tests (figure 13). A nanoprinting lithography technology was applied to nanoimprint-assisted shear exfoliation to generate ultrathin monolayer and few-layer MoS₂ structures [96].

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Growth of MoS₂ on epitaxial graphene (EG) was also reported [97, 98]. Authors report the ability to precisely control the thickness of two dimensionally rotationally commensurate grown MoS₂ heterostructures on EG through van der Waals epitaxial growth. In this van der Waals epitaxial growth method, the requirement for a transfer process is omitted, with the synthesis of complex 2D heterostructures. Additionally, it was also reported that the rotational commensurability observed between the EG and MoS₂ layers is driven by the energetically favourable alignment of the lattices, thereby resulting in perpetually strain-free MoS₂.

MoS₂ nanoparticles with excellent biocompatibility and capacity to carry significant loads for simultaneous chemotherapy drug delivery and tumor photothermal therapy have been produced using a bottom-up hydrothermal method (figure 14). For the single-step hydrothermal decomposition, sodium molybdate and cystamine dihydrochloride were used as precursors, with hydrazine hydrate used as a reductant for MoS₂ nanoparticle growth. In the process of hydrothermal synthesis, concomitant grafting of a polyvinyl pyrrolidone (PVP) coating onto MoS₂ was achieved due to the chelating-coordinating effect between PVP and Mo. The functionalisation significantly enhanced the colloidal stability of nanoparticles in physiological media. Thus-synthesised MoS₂ nanoparticles showed an exceptionally high photothermal-conversion efficiency and excellent ability to withstand photothermal degradation under near infrared irradiation [99].

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Three distinct plasma processes were studied to gain better understanding of the relative efficiency of plasma assisted methods for the synthesis of MoS₂ [108]. Results from this study indicate that processes involving dilute remote H₂S plasma (4%) and direct H₂S plasma (without dilution) may result in more effective synthesis of MoS₂. Findings from this study hint that a critical parameter which affects the synthesis pathways would be the presence of hydrogen radicals produced in the discharge that provide a means to reduce the MoO_x film and lower the energy barrier for further reactions. Additionally, plasma enhanced growth from the vapour phase was also demonstrated through the introduction of a volatile vapour phase of MoO₃ with the H₂S plasma. This resulted in uniform growth of few-layered MoS₂ on substrates at low temperatures bordering at 400 °C. The third and final method cited in this study for low temperature MoS₂ synthesis was through cyclical sputtering of Mo followed by a H₂S plasma immersion process.

Sharma et al studied the conditions of low-temperature large-area plasma-enhanced ALD of 2D MoS₂ with thickness control and tuneable morphology [109]. In this work, control over low temperature synthesis of monolayer-to-multilayer thick MoS₂ slabs was demonstrated by the authors through plasma enhanced ALD techniques. It is worth noting that on top of the ability to precisely tailor the morphologies of the deposited layers through varying the process temperatures within a wide operating regime from 150 °C–450 °C, a good control of the layer thickness characteristic of typical ALD processes is maintained. Good control of morphologies and thicknesses is further complemented by highly-desirable wafer scaled uniformity.

Tao et al reported the growth of wafer-scale MoS₂ monolayers using magnetron sputtering [110]. A novel process for the synthesis of wafer-scaled atomic MoS₂ layers on an array of different substrates through plasma magnetron sputtering was demonstrated by the authors. The MoS₂ films were grown at relatively high temperatures in the excess of 700 °C using Mo targets sputtered in a vapourized sulphur ambient containment facility. The vapourization of sulphur was made possible through a heating element encapsulating the sulphur container before it is directed into the chamber. Materials characterization shows that the fabricated MoS₂ are highly uniform, crystalline, and homogeneous. Electrical characterization also indicates p-type semiconducting character which is in contrast to the CVD fabricated MoS₂ films which are known to be n-type in nature.

Jeon et al produced MoS₂ layers using CF₄ plasma [111]. In this work, Mo sulphurization was employed for the synthesis of 2D MoS₂ thin films in an inductively coupled plasma (ICP) chemical vapour deposition reactor. The authors explored the potential for controlled etching of six-layer MoS₂ through the employment of fluorocarbon based (CF₄) plasmas typically used in plasma etch processes. It was eventually demonstrated that CF₄ indeed serves as a favourable feedstock for etching of MoS₂, with good ability to control layer thickness of MoS₂ thin films.

There is a wide range of pathways for fabrication of nanostructured molybdenum disulphide nanoparticles and nanocomposites. Among them, those based on high-pressure arc discharges offer several notable advantages. For one, the production yield in arc discharges is relatively high, whereas the level of defects in thus-produced nanoparticles is very small since their synthesis takes place in the very close proximity to a high-pressure arc column, where the temperatures reach in excess of 3000–4000 K [112, 113, 116]. Furthermore, nanomaterials fabricated using this method typically display high flexibility, and as a consequence greater mechanical strength properties compared to similar nanostructures produced via other methods [10, 11, 23]. These and other advantages have led to the extensive use of synthesis approaches based on arcs for growth of single wall carbon nanotubes not only at laboratory but also at industrial scales [10, 11, 24–26].

A typical arc discharge-based setup is shown in figure 15. In this set-up configuration, an anodic arc is generated in helium at approximately half the atmospheric pressure, with the arc current of below 100 A. The substrate is kept approximately 1–2 cm away from the arc source. Setups of this type could be magnetically enhanced, or work without an external magnetic field. Similar technology was used to fabricate hollow MoS₂ nanoparticles with ultra-low friction and wear [114]. An atmospheric-pressure plasma torch system was used for treatment of MoS₂–N₂ composites [117]. Examples of more complex MoS₂ nanoparticle-containing composites, such as TiN films with embedded MoS₂ fullerenes, have also been successfully produced by employing a combination of cathodic arc reactive evaporation and supersonic cluster beam deposition [115]. The process resulted in films assembled from clusters, where MoS₂ nanocages and nanostructures were successfully preserved and incorporated within the TiN matrix. Even at very low concentrations, the entrapped MoS₂ nanocages were shown to significantly alter the nanotribological characteristics of the TiN matrix, as shown using by atomic force microscopy.

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Discharges in liquids could produce high-quality complex nanostructures. An arc discharge generated between a cathode and anode made of graphite and molybdenum carrying MoS₂ microparticles immersed in de-ionized water, respectively, it was possible to produce molybdenum disulphide nanoparticles closely resembling the structure of closed caged fullerenes. High resolution microscopy confirmed that thus-produced polyhedral fullerene-like particles had a size of 5–15 nm in diameter and were typically made up of two to three layers of MoS₂. These nanoparticles were formed by seamless folding of MoS₂ fragments [118].

After synthesis, MoS₂ samples could be post-processed and trimmed in various reactive environments, i.e. in plasma [119]. As an example, flat planar samples can first be deposited on a substrate as a polycrystalline phase with average grain sizes in the order of hundreds of nanometres. The homogeneous as-grown MoS₂ films can then be processed with low powered (~25 W) Ar plasma at low temperatures of around 150 °C for 20 min. The films are observed to 'scroll up' from the edges as indicated in the schematic presented in figure 16 once the exposure duration to the Ar plasma was increased to 40 min. The observed heights of these nanoscrolls fabricated through the given plasma process range from a few to tens of nanometres. In this process, Ar plasma is thought to play a role in deconstructing the MoS₂ lattice by the removal of sulphur atoms located at the material–air interface when the kinetic energy of the impinging incident Ar ions are greater than the binding energy of Mo–S in the bulk.

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The dangling bonds created in this process are unable to be saturated due to the inert nature of Ar in the processing environment, which results in the creation of 'out-of-plane' strain. The additional strain induced from this collective process causes the rolling/scrolling of a single layer of MoS₂ starting from the edges. While the process of rolling is ongoing, previously formed scrolls are still continuously exposed to Ar plasma. Some of the exposed S atoms may also be removed in this state (indicated by the yellow balls in figure 4) and expedite the scrolling process through the formation of covalent bonds.

Successful application of plasma-based processes for the fabrication and treatment of MoS₂ composites has been demonstrated in a number of studies [120]. One of the better examples illustrating the simplicity and efficiency of plasma-based techniques is in the exploitation of a remote hydrogen process to induce S related vacancies on the basal plane of monolayer crystalline MoS₂. This process was reported to generate a high density of S vacancies while maintaining the structural integrity and overall morphologies of the MoS₂ monolayers as shown in figure 17(a). The generated defects resulting from the high density of vacancies due to the remote hydrogen plasma process can then be tuned in terms of magnitude accordingly through modulation of process parameters. The ability to tune the density of defects has critical implications on hydrogen evolution reactions as illustrated in the results presented by the authors from spectroscopic and electrical measurements. The H₂ plasma processed MoS₂ also serves as an excellent testbed for study of the dependence of material properties based on defects in transition metal dichalcogenides that brings information on potential for future disruptive novel applications including optoelectronic and magnetic devices [120, 121].

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Successful application of N₂ plasma for nitrogen doping of MoS₂ nanostructures was recently demonstrated (figure 17(b)). After N₂ plasma exposure, the group analysis of the surface chemistry of the resulting MoS₂ material indicates that N is prone to typically form a covalent bond with Mo through chalcogen substitution of S. Additionally, it was further pointed out that the N concentration in MoS₂ can be tuned precisely through varying duration of exposure to N₂ plasma. Results from electrical characterization further indicate that N acts as a p-type substitutional dopant in MoS₂ [122].

Qian et al performed plasma-enhanced dielectric deposition of single-layer MoS₂ with low damage using remote N₂ plasma treatment [123]. In this work, the authors present a pioneering report on the utilization of remote N₂ plasma for promotion of dielectric deposition of single-layer MoS₂. It was found that N₂ and O₂ plasmas tend to cause defects in MoS₂ albeit in different ways. As an example, it was shown that single layered MoS₂ is notably more stable in N₂ plasma as compared to O₂ plasma. This is likely due to the fact that O₂ plasmas cause defects primarily through oxidation of MoS₂ surfaces where defects are already present. These defects usually are present at flake edges which get oxidized rapidly, and it is observed on the macroscopic scale that this has no dependence on the thickness of MoS₂. For defect formation in the case of N₂ plasmas however, defects are created primarily through strain and distortion effects of the MoS₂ layers after adsorption of N on the surface. Since there is known to be a relatively strong MoS₂–substrate interaction coupled with the relative chemical inertness of MoS₂ in N₂ plasma, it is observed that single-layered MoS₂ exhibit excellent stability in the presence of N₂ plasma. This remains the case even after long term exposure to N₂ plasma where only stable point defects are observed.

Plasma treatment of surface properties of the ultrathin layered MoS₂ is a convenient tool for their functionalization and modification [124]. As reported, O₂ plasma treatment is suggested as a method to control the thickness as well as the electronic band structure of MoS₂ films. This could be enabled through the adoption of a low intensity ICP source, where the effects of the chemical reaction on the MoS₂ surface are relatively mild but still sufficient to induce desired alterations in structural and electronic properties of these materials. In order to do this, the authors first subject virgin MoS₂ to O₂ plasma for a few seconds. The samples are then exposed to ambient air, and subjected to O₂ plasma again, before being exposed to air once more and characterized. The schematic illustration of the process is shown in figure 18. Through this method, exposure to air causes weakening of Mo–S bonds. As a result, subsequent to air exposure, only 4 s of O₂ plasma exposure is required for complete removal of 1L of MoS₂. Comparatively, a 12 s treatment time is required to completely etch off 1L of MoS₂ if exposure to air was not performed intermediately. This study effectively demonstrates the ability to precisely control over layers in the MoS₂ material through modulation of duration of exposure to plasma.

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Mild oxygen plasma treatment was used to improve the electrical performance of MoS₂ [13] to repair the structural defects and improve the electron mobility of monolayer MoS₂ by up to an order of magnitude. This is attributed to the easy chemical bonding of oxygen with MoS₂ at sulphur vacancy sites. An interesting and very convenient method for tuning the properties MoS₂ by Ar plasma was also demonstrated recently [125] using a technology for the layer ordered etching of MoS₂ nanosheets. What is most notable of this proposed method is the ability of the complete removal of the top layer of MoS₂ with the bottom layer remaining basically unadulterated. This allows one to fabricate 2D heterostructures with periodic single and bilayered MoS₂.

The electronic transport properties of FETs based on MoS₂ of various layer thicknesses can also be tailored via controlled exposure to oxygen plasma [126]. In this case, high density of defect sites can be induced by O₂ plasma, which allows for devices employing up to eight layers of MoS₂ to have electronic properties that can be tuned from a semiconductor to a complete insulator. However, it is also worth mentioning that the time required for conversion to a fully insulating material depends on the number of layers inherent in the presented samples.

Cancer therapy is one of the most important applications of MoS₂ nanostructures, particularly in photothermal therapy. Recently, one-pot synthesis of MoS₂ nanoflakes through a hydrothermal method was reported (see figure 19). Thus-produced MoS₂ nanoflakes possessed degradation properties that are critical for many biomedical applications. Poly(acrylic acid) was used as a chemical facilitator that enabled decoration of MoS₂ nanoflakes with polyethylene glycol (PEG), as well as playing an important role in controlling degradation of the MoS₂ nanoflakes. The PEG-ylated hybrid nanoflakes (MoS₂ PPEG) also displayed superior stability when exposed to different media, coupled with exceptional photothermal properties. Interestingly, significantly different degradation rates were observed under different conditions. Rapid degradation of MoS₂-PPEG was observed in neutral solutions, whereas the degradation was somewhat slower in under acidic conditions that are typical of tumour microenvironment. Results from this study indicate that the major degradation byproduct of MoS₂-PPEG is water soluble Mo-based ions. Favourable in vitro biocompatibility of MoS₂-PPEG was demonstrated with cytotoxicity and haemolysis studies. Therefore, with the favourable photothermal performance presented, it can be further suggested that MoS₂-PPEG is a potential candidate for in vivo suppression of tumour growth. Finally, the decreased detectable content of MoS₂-PPEG in organs (and elemental Mo in urine) of a murine model indicate suitable level of degradability of MoS₂-PPEG and subsequent excretion of degradation products, both of which are critical for translation to clinical applications [141].

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It was also recently demonstrated that ultra-small, activated MoS₂ nanodots could also be efficient for the photothermal therapy [94]. A single-step bottom-up approach was adopted by the authors to develop theranostic agents with good clearance based on ultra-small MoS₂ nanodots. Specifically, this process involves solvothermal decomposition of ammonium tetrathiomolybdate. The MoS₂-GSH nanodots obtained after exposure to GSH exhibited hydrodynamic diameters under 10 nm without aggregation in various buffers. While showing no significant effects in terms of in vitro toxicity, the MoS₂-GSH nanodots also exhibit strong near-infrared (NIR) spectral absorbance [142].

This is highly desirable since this characteristic could potentially induce phenomenal photothermal ablation of cancer cells. In a murine model, efficient tumour accumulation of the MoS₂-GSH nanodots upon introduction through intravenous (IV) injection was observed through photoacoustic imaging. This phenomena was substantiated by the analysis of the biodistribution of elemental Mo. In comparison to conventional MoS₂ with nanoflakes of larger sizes, the MoS₂-GSH nanodots exhibited ultra-efficient clearance from the body through urine, where a vast majority of the injected dose was excreted within seven days. Additionally, photothermal ablation of tumours in mice was then studied, with the MoS₂-GSH nanodots showing superior therapeutic efficacy compared to other types of nanodots. This landmark study provides further evidence for the potential of MoS₂ nanoparticles as efficient agents for direct tumour treatment, with an added benefit of being rapidly degraded and removed from the body which should minimise the potential for long-term toxicity. This makes it a promising candidate for cancer theranostics [94].

Flower-like MoS₂ nanoflakes with high colloidal stability and ultra-low cytotoxicity can be synthesized through a modified hydrothermal method and modification with lipoic acid-terminated polyethylene glycol (LA-PEG) [143]. It is demonstrated that the nanoflakes exhibited commendable abilities to induce high temperatures, with good photothermal stability and conversion efficiencies upon irradiation with an NIR laser (808 nm). The authors also studied the in vitro photothermal effects of MoS₂-PEG nanoflakes with varied concentrations under different power densities of the incident 808 nm laser radiation. Results from this study show that low concentration of the MoS₂ nanoflakes under a low powered NIR laser irradiation display photothermal efficiency that is sufficient to kill cancer cells. It is expected that in vivo destruction of cancer cells could also be made possible through irradiation induced photothermal effects from the MoS₂-PEG nanoflakes (figure 20).

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The rapid proliferation of 3D printing techniques in biomedical fields have enabled successful fabrication of novel bifunctional MoS₂-containing scaffolds (MS-AKT scaffolds) through a hydrothermal complemented process [144]. MoS₂ nanosheets were grown on the strut surface of bioceramic scaffolds in a typical hydrothemal process. The presence of nanosheets on the surface of the scaffold enables its application in photothermal therapy, where upon exposure and irradiation from NIR sources, temperatures of the MS-AKT scaffolds can increase rapidly. This effect from temperature increment can be precisely controlled by variation of the MoS₂ content, laser power densities, as well as sizes of the MS-AKT scaffolds. This work illustrates how the photothermal temperature may have the potential to inhibit tumour growth, and significantly reduce the viability of osteosarcoma and breast cancer cells in vivo. Additionally, the MS-AKT scaffolds are found to promote in vivo rapid proliferation and osteogenic differentiation of bone mesenchymal stem cells and induce bone regeneration. This multifunctional scaffold that offers strategies in simultaneously treating tumours and facilitating bone growth is therefore has the potential to become a game changer in clinical treatment of tumour-induced bone defects (figure 21).

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Diagnostics is a critical part of a successful oncotherapy. To that effect, functionalization of single-layered MoS₂ nanosheets (NS) with fluorescent quantum dots (QD) and arginine–glycine–aspartic (RGD) containing peptides have been shown to result in low dimensional (0D–2D) RGD-QD-MoS₂ NS with remarkable fluorescence, photothermal conversion and cancer-targeting properties that can serve a plethora of applications in the biomedical field [145, 146]. The authors show how targeted fluorescent imaging and photothermal therapy of human cervical carcinoma (HeLa) cells may be enabled through the engineering of RGD-QD-MoS₂ NS as a theranostic agent. Using a murine model, effective fluorescent imaging and a full eradication of HeLa tumours through photo-thermal irradiation of RGD-QD-MoS₂ NS using a low powered NIR laser was shown. RGD-QD-MoS₂ NS were found to preferentially accumulate at tumour sites. This is made possible through RGD-integrin targeting and the enhanced penetration and retention (EPR) effect. Coupled with minimal reported toxicity effects to living organisms, RGD-QD-MoS₂ NS has exhibit significant potential as a dual-functional theranostic agent for cancer therapy and imaging (figure 22).

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A nanoplatform consisting of an aptamer (a molecule that selectively binds to another biomolecule) and PEG conjugated with MoS₂ NS with Cu_1.8S nanoparticles (ATPMC) has also shown good potential for applications in targeted therapy and medical imaging [147]. Examples of the latter include photoluminescence imaging, photoacoustic imaging, as well as in vitro and in vivo tumour cells imaging through photothermal methods. ATPMC also facilitates selective delivery of gene probes to detect intracellular microRNA that is not usually expressed in cancer cells, as well as for delivery of drugs such as doxorubicin (DOX) which is commonly employed for chemotherapy. Additionally, it is worth noting that the synergy between MoS₂ and Cu_1.8S provides the ATPMC platform with exceptional photothermal conversion efficiencies [148].

Fast targeted delivery of drugs to tumour cells is a critical factor in cancer and other types of therapies. Functionalized MoS₂ nanosheets as a multi-functional drug carrier for combination treatment of cancer were recently fabricated and tested [149]. MoS₂ was first synthesized through exfoliation from the bulk; functionalization with LA-PEG using thiol reaction was then performed to increase biocompatibility and physiological stability of the material. 2D MoS₂-PEG NS exhibit prominent NIR absorbance. The uniquely large surface area-to-mass ratio of MoS₂ nanosheets (owing to their atomically-thin structures) enables the high loading efficiency of therapeutic molecules including typical chemotherapy drugs such as DOX, 7-ethyl-10-hydroxycamptothecin (SN38), and a photodynamic agent chlorine e6. In addition to showing minimal toxicity to cells, MoS₂-PEG may also be implemented in combined photothermal and chemotherapy after loading with doxorubicin. This was demonstrated both using in vitro cell culture experiments, but also in vivo using a murine tumour model, with high level of anti-cancer activity arising from the synergistic coupling of MoS₂-EG and DOX following both intratumour or IV administration [35, 149].

Modification of surfaces of MoS₂ NS with copolymers through the fusion of mussel inspired chemistry and single-electron transfer living radical polymerization can be performed using 2-methacryloyloxyethyl phosphorylcholine (MPC) and itaconic acid (IA) as monomers. It was shown that the MoS₂-PDA-poly(MPC-IA) nanocomposites exhibited promising dispersability and biocompatibility. The drug loading capabilities and controlled drug release characteristics of MoS₂-PDA-poly(MPC-IA) towards cis-diamminedichloroplatinum commonly used in chemotherapy was also studied. It was then determined that the drug loading capacity in MoS₂-PDA-poly(MPC-IA) nanocomposites reach up to 55.26%. This indicates that the proposed strategy for fabrication of the aforementioned MoS₂ based nanocomposites may potentially have significant applications in cancer related therapeutic fields [150].

This interesting platform allows efficient control of the drug delivery and release [91]. Functionalized MoS₂ NS that have been developed as a chemotherapeutic drug carrier for NIR photothermal-induced drug delivery can also be fabricated through the decoration of MoS₂ NS with chitosan. This promotes the integration of both photothermal therapy and chemotherapy into a consolidated all-in-one system for cancer therapy. Controlled release of DOX can be triggered via photothermal effects using irradiation by an 808 nm NIR laser. As compared to standalone chemotherapy or photothermal therapy methods, in vitro and in vivo tumour ablation studies suggest potential synergistic therapeutic effects resulting from the combined treatment.

During embryonic development, blood vessels are first developed via vasculogenesis, after which point new blood vessels grow from existing vessels to accommodate organism growth and development, as well as wound repair in the process called angiogenesis. This process is tightly controlled through specific signalling pathways, and generally its activity declines with age. However, activation of signalling pathways during tumourigenesis is a critical step in the transformation of benign tumours into malignant counterparts, where the formation of additional blood vessels ensures effective delivery of oxygen and nutrients to the growing tumour and removal of waste products. To initiate and stimulate this process, cancer cells release various growth factors and proteins. Not surprisingly, a number of antiangiogenic drugs have been developed to halt blood supply from the tumours, however when introduced systemically, these drugs are often ineffective due to dilated and often abnormally structured blood vessels within the tumour. Furthermore, the often show detrimental side effects in vivo. Nanomaterial-based therapies and drug delivery platforms offer several advantages, including relatively high capacity for drug loading and controlled release of drugs into tumour microenvironment, higher blood half-life and lower cyto-, organ and systemic toxicity of these structures [151]. For instance, when introduced into a chicken embryo as part of a HeLa cell-extracellular matrix (ECM) gel suspension, MoS₂–ZnO nanocomposites have been shown to significantly reduce the expression genes associated with angiogenesis, i.e. VEGF and VEGFR2, preventing vascularization into the tumour intima [152]. Furthermore, exposure to the MoS₂–ZnO nanocomposite were also shown to activate caspase-3, a cysteine-aspartic acid protease known for its role in apoptosis.