**4. Chiral assemblies of achiral plasmonic nanoparticles**

Consider sensing approach basing on geometrical chirality of chiral molecules. Physically, the generation of chiroptical response is due to both exciton-plasmon interaction, as described in previous section, or plasmon-plasmon coupling between achiral nanoparticles, arranged in a chiral superstructure [50]. In the latter case, the molecules play a role of a template and define handedness of the resulting assemblies. Eventually, the presence of the chiral molecules can be detected by the appearance of the CD signal.

Currently, several techniques were used to arrange plasmonic metal nanoparticles in chiral superstructures. As an example, DNA molecules can serve as such a template and chiral DNA-based structures are considered in recent reviews [51–56]. This method is often called "DNA origami." Besides, promising results have been achieved using peptide-directed assembly of gold nanoparticles into single-helix [57, 58] and double-helix superstructures [59, 60] (see **Figure 5**).

In order to arrange metallic nanoparticles in chiral assemblies, cholesteric liquid crystals were also used by the authors [61–63]. The elongated nanofibers obtained in cholesteric liquid crystalline mesophase are demonstrated in **Figure 6** [62]. Firstly, silver nanoparticles (2.5 nm in size) were formed and then their helical ordering was resulted due to the specific interactions of ligand molecule's functional thiol- groups with the surface atoms of silver nanoparticles. This process was resulted in hybrid spirals formation. In the case of a thiocholesterol ligand, concentrated organosols of such aggregates have high optical activity, as demonstrated by CD spectra. The optical spectra of these systems exhibited the absorption at about 430–450 nm, attributed to the LSPR bands of silver nanoparticles, and long-wavelength absorption at 700–1000 nm, which is characteristic of linear aggregates. This near infrared region is suitable for in vivo imaging and biosensing.

Anisotropic plasmonic nanoparticles, such as nanorods, offer some additional advantages, including better near-field focusing and high sensitivity to relative particle orientation [60]. The generation of optical activity in a dimer of gold nanorods was theoretically investigated. It was shown that hybrid plasmon modes, binding and antibinding, contribute to the CD signal [64]. Increased chirooptic activity was shown also by dimers and larger aggregates of gold nanorods initiated by immobilized DNA oligomers during PCR [65], which made it possible to detect DNA attomols [66]. The chiral response arose due to a slight twist between the nanorods. In the process of self-assembly, both enantiomers were formed, but one

**47**

**Figure 5.**

*Nature.*

**Figure 6.**

*Chiral Hybrid Nanosystems and Their Biosensing Applications*

of them was thermodynamically more favorable. Glutathione molecules supported by cetylammonium bromide micelles directed the self-assembly of gold nanorods

*TEM images of silver nanoparticle aggregates stabilized by thiocholesterol (after 24 h storage in mesophase): (a) general view, (b) internal structure, and (c) the formation scheme of silver-thiocholesterol chiral 3D-aggregates. Reproduced with permission from Shabatina et al. [62], Copyright 2013 Springer.*

A strong chiroptical signal can be generated by plasmon nanorods assembled into a three-dimensional spiral structure by supramolecular fibers, such as anthraquinone based oxalamide [68]. The DNA origami approach allowed you to adjust the chiro-optical response by carefully controlling of the plasmonic superstructure. Dynamic switching between different configurations of the nanorod spirals led to a

Other biomolecular matrices also can be used to order plasmonic nanoparticles in three-dimensional chiral assemblies, such as proteins or their aggregates. So, it

and the formation of chiral nanochains with end-to-end contacts [67].

*Chiral assemblies of gold nanoparticles and DNA origami in left- and right-handed nanohelices:* 

*(a) schematics, (b) TEM image. Reproduced with permission from Kuzyk et al. [53], Copyright 2012 Springer* 

change in the chiro-optical response [69].

*DOI: http://dx.doi.org/10.5772/intechopen.93661*

*Chiral Hybrid Nanosystems and Their Biosensing Applications DOI: http://dx.doi.org/10.5772/intechopen.93661*

#### **Figure 5.**

*Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis*

5 × 10−10 ng/mL (1.5 × 10−20 M) has been determined.

sensitivity and selectivity in practical applications.

appearance of the CD signal.

**4. Chiral assemblies of achiral plasmonic nanoparticles**

[57, 58] and double-helix superstructures [59, 60] (see **Figure 5**).

region is suitable for in vivo imaging and biosensing.

in living cells with a detection limit of 0.2 mM has been demonstrated [47]. The results of telomerase activity study were reported: a limit of detection as 1.7 × 10−15 IU in a single HeLa cell was reached [48]. **Figure 4a**–**c** demonstrates another general approach to the formation of sensitive plasmonic dimers by using antibody-antigen interactions. For the chiroplasmonic detection of an environmental toxin, microcystin-LR, and a cancer biomarker, prostate-specific antigen (PSA), a silver-gold nanoparticle heterodimer was used [32]. The PSA limit of detection as

Recently, the detection of DNA molecules (with concentrations below 100 pM) located in the gap of two gold nanoparticles was successfully demonstrated [49]. The effects of the particle's gap size, shape, etc. were analyzed. In this way, for the detection of small chiral molecules, enzymes and proteins plasmonic dimers can be used. This approach is highly promising for biomedical applications such as biorecognition and intracellular detection. The use of DNA contributes to high

Consider sensing approach basing on geometrical chirality of chiral molecules. Physically, the generation of chiroptical response is due to both exciton-plasmon interaction, as described in previous section, or plasmon-plasmon coupling

between achiral nanoparticles, arranged in a chiral superstructure [50]. In the latter case, the molecules play a role of a template and define handedness of the resulting assemblies. Eventually, the presence of the chiral molecules can be detected by the

Currently, several techniques were used to arrange plasmonic metal nanoparticles in chiral superstructures. As an example, DNA molecules can serve as such a template and chiral DNA-based structures are considered in recent reviews [51–56]. This method is often called "DNA origami." Besides, promising results have been achieved using peptide-directed assembly of gold nanoparticles into single-helix

In order to arrange metallic nanoparticles in chiral assemblies, cholesteric liquid crystals were also used by the authors [61–63]. The elongated nanofibers obtained in cholesteric liquid crystalline mesophase are demonstrated in **Figure 6** [62]. Firstly, silver nanoparticles (2.5 nm in size) were formed and then their helical ordering was resulted due to the specific interactions of ligand molecule's functional thiol- groups with the surface atoms of silver nanoparticles. This process was resulted in hybrid spirals formation. In the case of a thiocholesterol ligand, concentrated organosols of such aggregates have high optical activity, as demonstrated by CD spectra. The optical spectra of these systems exhibited the absorption at about 430–450 nm, attributed to the LSPR bands of silver nanoparticles, and long-wavelength absorption at 700–1000 nm, which is characteristic of linear aggregates. This near infrared

Anisotropic plasmonic nanoparticles, such as nanorods, offer some additional advantages, including better near-field focusing and high sensitivity to relative particle orientation [60]. The generation of optical activity in a dimer of gold nanorods was theoretically investigated. It was shown that hybrid plasmon modes, binding and antibinding, contribute to the CD signal [64]. Increased chirooptic activity was shown also by dimers and larger aggregates of gold nanorods initiated by immobilized DNA oligomers during PCR [65], which made it possible to detect DNA attomols [66]. The chiral response arose due to a slight twist between the nanorods. In the process of self-assembly, both enantiomers were formed, but one

**46**

*Chiral assemblies of gold nanoparticles and DNA origami in left- and right-handed nanohelices: (a) schematics, (b) TEM image. Reproduced with permission from Kuzyk et al. [53], Copyright 2012 Springer Nature.*

#### **Figure 6.**

*TEM images of silver nanoparticle aggregates stabilized by thiocholesterol (after 24 h storage in mesophase): (a) general view, (b) internal structure, and (c) the formation scheme of silver-thiocholesterol chiral 3D-aggregates. Reproduced with permission from Shabatina et al. [62], Copyright 2013 Springer.*

of them was thermodynamically more favorable. Glutathione molecules supported by cetylammonium bromide micelles directed the self-assembly of gold nanorods and the formation of chiral nanochains with end-to-end contacts [67].

A strong chiroptical signal can be generated by plasmon nanorods assembled into a three-dimensional spiral structure by supramolecular fibers, such as anthraquinone based oxalamide [68]. The DNA origami approach allowed you to adjust the chiro-optical response by carefully controlling of the plasmonic superstructure. Dynamic switching between different configurations of the nanorod spirals led to a change in the chiro-optical response [69].

Other biomolecular matrices also can be used to order plasmonic nanoparticles in three-dimensional chiral assemblies, such as proteins or their aggregates. So, it

**Figure 7.**

*Composite α-synuclein fiber with 3D chiral arrangement of Au nanorods: (a) TEM image, (b) cryo-TEM tomography reconstruction, (c) extinction, and (d) CD spectra of Au nanorods monitored 30 min after the addition of 30 μL of purified brain homogenates from healthy (black) and Parkinson-disease-affected (red) patients. Adapted with permission from Kumar et al. [60], Copyright 2018 National Academy of Sciences.*

was reported that amyloid fibrils of α-synuclein CD were detected using helically arranged gold nanorods (see **Figure 7**) [60]. At the same time, chiro-optical activity was not detected when only α-synuclein monomers were present. This technique can be further expanded to detect infectious recombinant prions.

There are cases of aggregation of plasmonic nanoparticles, leading to the sharp optical changes upon initiation by only one enantiomer. D-glutamic acid led to the aggregation of gold nanoparticles coated with CTAB, which followed by a significant change in color, while for the L-enantiomer there were practically no changes [70]. Similarly, the enantioselective detection of D-cysteine by silver nanoparticles was recently demonstrated in the solution and in the special bacterial cellulose matrix [71].
