GNWs can be used as important building blocks for nanotechnology because of their excellent physiochemical properties. As for unusual gold nanostructures, 70% of the gold atoms of ultrathin GNWs are at the surface, which make them an excellent nanoelectrode candidate in electrochemical applications, such as pressure sensors, DNA detector, interconnects and nanoelectrodes [8].

Meanwhile, GNWs could provide high current densities, high signal to noise ratio and low double layer capacitance. These properties are important for sensing applications [17]. As the GNWs are not thermally stable, mild heating could make them disintegrate into nanoparticles. Therefore, GNWs become stable with the help of an organic molecule layer, such as oleylamine (OA). However, as shown in Figure 1, the organic layer greatly deteriorated the electron transport of GNWs, whose resistance increases from 10³ Ω to 10⁶ Ω [15]. Catalytic ability can further be reduced by the organic layer [18]. So, removal of the organic layers is essential for practical applications. For example, the use of low concentration of sodium borohydride (NaBH₄) solution removed the molecular adsorbates on GNWs immediately [19]. Thus, the pure GNWs without protective layers have fantastic conductivity and catalytic ability, and they can be greatly involved in sensing and catalytic fields.

The understanding of fracture behaviors and corresponding mechanisms is essential for ultrathin gold nanowires’ potential in nanoscale electrical and mechanical devices [20]. It not only helps in design and fabrication of next generation interconnects, but also advances our understanding of nanoscale mechanics and coupling of electrical and mechanical properties [14,21]. The stability of GNWs pressure sensors is greatly dependent upon the fracture behavior of GNWs. With the greatly developed cold welding techniques for ultrathin gold nanowires, the picking-up and clamping procedures are realized without damaging the sample structures and morphologies which make the systematic study of tensile fracture behavior for sub-20 nm gold nanowires available. As gold is considered one of the most ductile metals, the ductile fracture of GNWs are observed with plastic deformation and a neck formed in the middle section before final fracture. However, the unexpected brittle-like fracture of GNWs are reported which are closely related to the twin structures of GNWs. Furthermore, the brittle fractures have higher engineering strength (0.929 GPa) than ductile fractures. The mechanism of brittle-like fractures is related to the misalignment of twin structures formed during the initial loading stage, which is different with the plastic deformation for the ductile fracture [14].

Furthermore, gold nanostructures with surface plasmons resonance have enabled surface enhanced techniques essential for trace level detection, such as surface enhanced Raman spectroscopy (SERS) and surface enhanced fluorescence (SEF) [22]. GNWs, as cylindrical nanostructures, have attracted great attention owing to the tunable longitudinal localized surface plasmon resonances (LSPRs), whose plasmon absorption band redshift with the increasing aspect ratio (length/diameter) [23]. LSPRs are the collective coherent oscillations of electrons in metallic nanostructures. The enhanced optical near-field due to plasmon excitation in GNWs is of great interest in both basic research and for applications as chemical sensors and optical spectroscopy [4,24,25]. Moreover, GNWs can easily self-assemble into a two-dimensional network structure with a variety of closely packed nanowires which serve as an active substrate in SERS [4]. As for SERS, both local field and radiative enhancement contribute to the SERS cross-section. Maximum SERS enhancement is induced at an intermediate wavelength between peak excitation wavelength and Raman vibrational frequency which results in simultaneous enhancement of incident and scattered photons [26]. While in SEF, the fluorescence cross-section on gold surface depends on the relative enhancements of radiative and non-radiative decay rates through amplifying the local photonic mode density and synchronous energy transfer to the metal. Therefore, quenching is induced when fluorophore is close to the gold surface, while Raman signal is significantly enhanced. As distance increases, fluorescence intensity reaches a maximum and then falls off while Raman signal decreases greatly.

Last but not least, the chirality of gold clusters is important for the development of asymmetric drugs, sensors and catalysts. The chirality of gold clusters are considered in four levels, which includes the chiral thiolate ligands, the arrangement of the ligands, the inherent chirality of cluster core and the cis/trans isomerism in the bridged Au-S binding motif. The crystal structure of Au₁₀₂ (p-MBA)₄₄ (Figure 2A) is thought of as a 49-atom Marks decahedron and additional 30 surface atoms split into two 15-atom subgroups on opposite sites. Fivefold symmetry is found for the core of the cluster, in which 19 short and two long units SR (AuSR)_x (x = 1, 2) protect the core. The crystal structure of Au₂₅ (2-PET)₁₈ consists of a Au₁₃ core with six dimeric units (Figure 2B) and the structure of Au₃₈ (2-PET)₂₄ consists of a face-fused bi-icosahedral Au₂₃ core which is protected by six dimeric and three monomeric units (Figure 2C,D). The bridged binding motifs SR-Au-SR adopts cis/trans geometry with other organic ligands. For the diametric units SR (AuSR)₂, the pseudochiral is considered for the central sulphur atom. With the development of high performance liquid chromatography (HPLC) and circular dichroism spectroscopy, the intrinsically chiral gold clusters are developed greatly for enantioseparation [27]. Furthermore, the Au₄₀ (2-PET)₂₄ clusters have Au₂₆ core, which is composed of two icosahedrons in contact. The intrinsically chiral ligands are inverted from the enantiomers at high temperature and ligand exchange reaction involves chiral ligands to increase optical activity. Furthermore, the chirality of gold clusters is used in catalysis and sensing fields because of the flexibility of the Au-thiolate interface [28]. Table 1 gives a list of properties of gold nanowires and their potential applications.

GNPs, with a diameter between 1 nm and 100 nm, have been extensively used in chemical and biological sensors because of their excellent physical and chemical properties. The unique optical property of GNPs is one of the reasons that GNPs attract tremendous interests from different fields of science, especially in the development of sensors. The spherical GNP solutions show a range of vibrant colors including red, purple and violet when the particle size increases, and they could be used to stain glass in ancient time. The intense color is caused by the strong absorption and scattering of ca. 520 nm light [29], which is the result of the collective oscillation of conduction electrons on the surface of GNPs when they are excited by the incident light. This phenomenon is known as surface plasmon resonance (SPR), and it depends greatly on particle size and shape. Thus, the SPR peak is tunable by manipulating the size of GNPs, and this property cannot be observed on bulk gold and GNPs with a diameter smaller than 2 nm. The SPR peak is not only sensitive to size and the shape, but also many factors such as protective ligand, refractive index of solvent, and temperature. The interparticle distance particularly shows great influence on SPR. Therefore, the red-shifting and the broadening of the peak are observed when GNPs are aggregated due to analyte binding. The color change of aggregated GNPs from red to blue is the principle of colorimetric sensing. A number of recent researches and reviews provide a detailed discussion on the factors that influence the SPR of GNPs [6,30,31,32,33]. The emitting of the SPR can be used for measuring electrical properties. When metal nanoparticles form 1D, 2D or 3D structures, the combining of surface plasmons from the neighbor nanoparticles results in new optical properties which depend on the extent of assembly. According to the work by Creighton et al. [34], different metal ions have different SPR band positions in the UV/Vis spectrophotometer.

Apart from absorption and scattering properties, GNPs also display fluorescence properties which could be utilized in sensor fabrication. Photoluminescence can be generated from GNPs under certain conditions, such as laser [35] and ultraviolet (UV) excitation [36]. GNPs can enhance or quench the fluorescence of fluorophore depending on the distance between the fluorophore and the particle [37]. Based on radiating plasmon model, Lakowicz suggested the absorption and scattering are related to the enhancing or quenching the fluorescence. As incident energy is dissipated by absorption and far-field radiation is created by scattering, larger GNPs are more likely to enhance fluorescence. Smaller GNPs are more likely to quench fluorescence because the scattering component is dominant over absorption [38]. Fluorescence is enhanced because the far-field radiation from the fluorophore is reflected back on itself. Hence, fluorescence can be quenched by fluorescence resonance energy transfer (FRET) [39], photoinduced electron transfer (PET) [40] or nanosurface energy transfer (NSET) [41] pathway.

In addition to the fluorescence property, GNPs can enhance Raman scattering, which leads to the development of SERS based sensing. Raman scattering is normally weak. The electromagnetic contribution to SERS is induced by the intense optical frequency field which originates from the plasmon resonance of GNPs, which can be used for single molecule detection [42]. The enhancement of Raman scattering depends on various factors including particle size, shape and aggregation. There are now two mechanisms to illustrate how SERS is enhanced, one is long-range electromagnetic effect and the other is short range chemical effect. The electromagnetic contribution to SERS is induced by the intense optical frequency field which originates from the plasmon resonances of GNPs, while the chemical mechanism is induced by the electron transfer between molecules and the surface. From electromagnetic, the enhancement factor is about 10¹¹, which can only be obtained at the interstitial sites between two particles or at outside sharp surface protrusions. As for single molecular detection, electromagnetic enhancement is not strongly enough, there should be chemical or other related enhancement to accomplish single molecular detection [43].

Please note that GNPs alone have limited application in sensing unless surface modification is performed. Careful selection and design of ligands strongly influence the sensitivity and selectivity of a sensor. Thiol-gold chemistry is well studied and has been widely used for the surface coating of GNPs. The strong S-Au bond (ca. 50 kcal·mol⁻¹) [44] allows effortless anchoring of a range of chemical species, regardless of their molecular sizes, to the surface of GNPs [1,45,46]. The hybrid materials, containing inorganic metal core and organic layer, show novel properties and can self-assemble into the desired structure, which could be essential for biosensing. Van der Waals’ force, electrostatic interaction and solvation force are important forces for tuning GNPs’ assembly [47,48,49,50]. However, the immobilization of chemical species also affects the stability of GNPs, as it changes the properties of the solid–liquid interface. In this way, GNPs may aggregate and the functionality may not be maintained. This could be solved by the addition of surfactant or stabilizer [51], or the optimization of ligand and GNPs. Table 2 summarizes potential applications based on some of the properties of GNPs.

The interaction of light with nanostructures is the focal domain of nanooptics. The general optical properties of metal nanostructures are significantly different from their bulk material because of the quantum size effect which is from discrete electron bands. When plane-wave lights excite a GNP, coherent oscillation of conduction electrons are induced by the oscillating electric field which leads to the accumulation of polarization charges on the surface of a GNP, known as LSPR [26,52,53,54,55]. The electric field of light interacts with the free electrons in the nanoparticles, leading to a charge separation and in turn the Coulomb repulsion among the free electrons acting as a restoring force pushes the free electrons to move in the opposite direction. Mie theory involves Maxwell’s equation to describe the LSPR for non-interacting GNPs, with the extinction cross-section, C_ext, which can be expressed in Equation (1) as: (1) where ε_m is the dielectric constant of the surrounding medium; ε_r and ε_i are the real and imaginary part of the dielectric function of particles; R is the radius of the GNP; and N is the electron density. The factor χ stands for the shape of the particle, and is assigned a magnitude of two for a spherical particle and can be 20 for particles with high aspect radio.

As for interacting particles, the plasmon resonance red-shifts and a lower energy absorption band appears, resulting from the interactions between GNPs: near-field coupling and far-field dipolar interactions. Furthermore, surface plasmons for non-spherical metallic nanostructures are shape-dependent. In particular, for GNWs the plasmon resonance splits into low- and high-energy absorption bands, one for the transverse mode around 515 nm and the other for the longitudinal mode whose position depends strongly on the aspect ratio [46,56,57]. In the case of gold nanorods, Gans theory describes the optical behavior according to Gan’s formula, the extinction cross-section C_ext in Equation (2) as: (2) where V is the volume of the particle; and P_j is the depolarization factor. The depolarization factor for the elongated particles can be described as: (3) (4) where e is the ellipticity as: (5)

The LSPR occurs when ε_r = −((1 − P_j)/P_j) ε_m, where P_j = P_longth for the longitudinal plasmon resonance and P_j = P_width for the transverse plasmon resonance. Small changes in the aspect ratio will change the plasmon band significantly.

GNWs are normally prepared by two methods, “bottom-up” and “top-down” methods. Bottom-up method is the self-assemble of small sized structures to form larger structures, while the “top-down” method is based on the reduction of large systems into smaller sizes [58]. Bottom-up methods are more popular which include template directed methods and non-template directed methods.

Since Faraday synthesized colloidal gold in 1857 [2], many efforts have been made to prepare GNPs in different sizes, shapes, solubility, and surface functionality, in order to fulfill the demands from various scientific fields. In most cases, GNPs are synthesized in solution phase by reducing gold salts in the presence of an appropriate capping agent that prevents particle aggregation.

Reducing tetrachloroauric acid (HAuCl₄) in water by sodium citrate, invented by Turkevich et al. [71] in 1951, has been the most popular method. This protocol typically prepares spherical monodisperse GNPs of 10–20 nm, while sodium citrate acts as both a reducing and capping agent. Frens later refined this method to synthesize GNPs of 16 nm to 147 nm by manipulating the ratio of HAuCl₄ to sodium citrate [72]. The problem of poor size and shape dispersion in large citrate-reduced GNPs (>50 nm) was solved by Perrault’s group [73]. Better quality of GNPs of 50–200 nm can be obtained using hydroquinone (HQ) as a reducing agent.

Aside from aqueous phase, GNPs can also be prepared in organic phase. In 1994, Brust et al. [74] introduced a breakthrough two-phase synthetic method to prepare 1–3 nm GNPs. HAuCl₄ is transferred into toluene using tetraoctylammonium bromide (TOAB) and reduced by sodium borohydride (NaBH₄) in the presence of alkanethiol. Hostetler et al. [75] extended the range of size of GNPs to 5.2 nm by carefully controlling the reaction temperature, the ratio of HAuCl₄ to alkanethiol, and the reduction rate. Other capping agents, such as phosphine [76] and TOAB [77], have been used to synthesize GNPs of diverse sizes and dispersities.

In addition to the bottom-up methods mentioned above, top-down methods, including laser ablation [78], are another way to obtain GNPs. The size and shape of prepared GNPs can be modified by many treatments, such as digestive ripening [79] and laser irradiation [78]. According to Table 4, the GNPs are generally stabilized with chemicals of low functionality, which limits their applications in sensing. Versatile molecules, such as protein and oligonucleotide, can be anchored on GNPs by ligand exchange process for the detection of a variety of analytes of interest. Summarized in Table 4.

For human healthcare and environmental monitoring, GNP based sensors have been extensively developed to detect metal ions. The strong interaction between metal ions and glutathione (GSH) is a common design concept for metal sensing. Beqa et al. [80] have reported a colorimetric and DLS assay for lead (II) ion (Pb²⁺) using GSH functionalized GNPs at pH 8. Aggregation of GNPs, induced by the chelation of Pb²⁺ via carboxylate groups, is detected by DLS with a detection limit of 100 ppt (0.4 nM). Other than river water sample, this sensing system has also successfully detected Pb²⁺ in paint and plastic toys, which extends its application. Pentapeptide (CALNN) has been used to stabilize GSH coated GNPs to detect Pb²⁺ in both aqueous solution and living cells [81]. High sensitivity (2.9 × 10⁻¹⁵ M Pb²⁺ per cell) has been achieved.

Apart from functionalizing uniform size GNPs, Weng et al. [82] has demonstrated the linkage of large and small L-cysteine coated GNPs as core-satellite by copper (II) ions (Cu²⁺) as shown in Figure 3. The self-assembly of core-satellite structure causes red shift of SPR peak and allows detection of Cu²⁺ in aqueous solution as low as 2.23 μM. Further, Cu²⁺ in living cells can be detected by a bovine serum albumin (BSA) coated GNPs fluorescent sensor [83]. The addition of Cu²⁺ binds with BSA and quenches the fluorescence of GNPs, which can be reversed by adding glycine. The limit of detection (LOD) was reported to be 50 μM. Another fluorescent sensor is fabricated to detect mercury (II) ions (Hg²⁺) by DNA functionalized GNPs [84]. The design is based on the interaction of thymine and Hg²⁺, which reduces the distance between the fluorescein and GNP and results in fluorescence quenching. GNPs coated with Raman reporter dye and cadmium (II) ion (Cd²⁺) sensitive polymers have been used as a SERS based sensor [85]. The presence of Cd²⁺ induces aggregation and activates the dye with 90-fold signal enhancement. Although the LOD is 1 μM, which is relatively low among SERS based sensors. This system allows the detection of Cd²⁺ in heavily colored samples.

However, relatively few researches have been carried out to develop GNP based sensors for anions. It is mainly due to the difficulty in designing receptors for anion. He et al. [86] have developed a 4′-(4-mercaptophenyl)-2,2′,6′,2′′-terpyridine zinc(II) complex (MPTP-Zn) coated GNPs colorimetric sensor for phosphate ion (PO₄³⁻) in aqueous solution. The design is based on binding of PO₄³⁻ to Zn metal complex in enzymatic reaction, rather than relying on the conventional hydrogen bonding and electrostatic reaction. Although the detection is rapid and highly selective, the LOD is reported to be 120 μM. Therefore, the relatively low sensitivity restricted the practical application of this system. Unlike common sensing approach, a colorimetric sensor for sulphide ion (S²⁻) by GSH functionalized GNPs is designed to make use of the anion-for-molecule ligand exchange reaction instead of the functionality of GNPs [87]. The partial replacement of GSH by S²⁻ caused aggregation with LOD of 5 μM.

Fluorescein isothiocyanate (FITC) labeled BSA has been coated on GNPs to detect both iodide (I⁻) and cyanide ion (CN⁻) in high salinity solution [88]. FITC is released and its fluorescence is restored during the binding of anion to GNPs. The LOD was 50 nM and 1 μM for I and CN, respectively, in the presence of various masking agents. CN⁻ is a popular analyte of interest. Lou’s group also contributed to the development of fluorescence sensing of CN⁻ based on the dissolution of GNPs [89,90]. Imidazole functionalized polyfluorene and polyacetylene were attached on GNPs, and LOD was reported to be 0.3 μM and 3 μM, respectively. SERS based sensing for CN⁻ has been developed considering the formation of hot spots during the aggregation of ascorbic acid functionalized GNPs in the presence of CN⁻ [91]. High sensitivity (110 ppt) is achieved with excellent discrimination against other metal ions and anions.

GNPs based sensors have been developed to detect biomolecules as well. Ligation chain reaction (LCR) based GNP aggregation is widely utilized in the design of DNA sensors. Yin’s group and Shen’s group have reported colorimetric LCR based systems with LOD of 0.1 × 10⁻¹⁸ M by DLS and 2 × 10⁻¹⁷ M by UV-Visible spectrometer, respectively [92,93]. GNP probes were ligated during hybridization of target strand, and the aggregation caused detectable color change after a number of thermal cycles.

As shown in Figure 4, Wang et al. [94] have explored the usage of toehold-mediated stand-displacement reaction with GNP fluorescence anisotropy signal enhancement in the development of a homogeneous single nucleotide polymorphism (SNP) detection assay. Fluorescein labeled DNA is detached during the hybridization of target DNA, resulting in low fluorescence anisotropy. The dynamic and kinetic difference allows distinguishing SNP from perfectly matched target strand. Florescent sensing of oligonucleotides can also be carried out by modifying GNPs with hairpin shaped molecular beacon (MB), which the fluorescence is quenched without the presence of target analyte. Xue et al. [95] have developed such a sensor for mRNA of signal transducer and activator of transcription 5B (STAT5B) that is related to the metastasis and proliferation of tumor cells. The conformation of MB is changed when hybridized with target, thus fluorescence is enhanced due to the increase in fluorophore-GNP distance. Similarly, bi-MB functionalized GNPs sensor detecting of two types of breast cancer related mRNA is reported [96]. Target analytes from 0.3 to 0.5 nM are stated as the LOD of this assay. Both systems successfully show fluorescence in living cells which are promising in early detection of cancer.

Some research contributes to the detection of smaller biomolecules. A colorimetric sensor for GSH has been developed based on the anti-aggregation of GNPs [97]. It has been reported that higher selectivity could be achieved by the use of anti-aggregation of GNPs, and the LOD is 8 nM. Plasmodium falciparum heat shock protein (PfHsp70), antigen for malaria parasite, is detected by a fluorescence competitive immunoassay using antibody coated GNPs [98]. Free antigen displaced the fluorophore labeled recombinant PfHsp70, thus fluorescence enhancement was observed. The LOD is estimated to be 2.4 μg·mL⁻¹ and this assay has detected antigen in human blood culture at a 3% parasitemia level. GNP-based sensors can also detect biological pathways. The monitoring of DNA assembly and enzyme cleavage is achieved by SERS based sensor [99]. DNA assembly creates hot spots for detection, while enzyme cleavage decreases the SERS signal. Thus, the whole process can be monitored by observing the changes in SERS signals.

The sensitivity of GNP-based sensors is influenced by various factors, including the analyte of interest, protective ligand and sensing approach. Some GNP-based sensors utilizing their optical properties are summarized in Table 5.