**3. Chiral molecules in the gap of dimers of plasmonic metal nanoparticles**

A similar chirooptical phenomenon is theoretically predicted for chiral molecules located in the gap of dimers of plasmonic nanoparticles for both resonant and nonresonant CD signals [27–30]. Strongly amplified electric field localized in the gap of such nanostructures results in a strong CD amplification. The enhancement factors up to 3000 can be expected for 5 nm gap. **Figure 3a,b** demonstrate the schematic image of the system and the correlation of CD enhancement with electric field in the gap [31].

This effect was experimentally observed in several systems of aggregated metal nanoparticles (NP), such as spherical gold nanoparticles conjugated to oligonucleotides [32–34], cysteine-modified gold nanorods [35, 36] and nanospheres [37, 38], as well as cholate-coated silver nanoparticle [39], etc. The CD signal is greatly enhanced by particle agglomeration, which leads to the formation of nanometer-sized gaps.

A demonstration of chiral biosensing based on the formation of asymmetric plasmon dimers has been reported recently [40]. The authors detected CD signal generated by self-assembly of gold nanorods using an antigen-antibody recognition reaction. The low detection limit for bisphenol A of 0.02 ng/mL was reached. To assemble nanoplasmon dimers with a tunable chiroptical response, the immobilization of highly specific complementary DNA primers on their surface were

#### **Figure 3.**

*Chiral molecules in the gap of a plasmonic dimer: schematics (top), (a) calculated CD enhancement factor for different gap size; (b) corresponding values of average electric field in the gap volume. Reproduced with permission from Nesterov et al. [31].*

**45**

**Figure 4.**

*American Chemical Society.*

*Chiral Hybrid Nanosystems and Their Biosensing Applications*

fulfilled [34]. Using this method and its modifications, various analytes were successfully being detected. For instance, self-assembly of silver ions was carried out with a detection limit of 2 pM by inducing the nanodimer assembly reaction [41]. By triggering the DNA-based chiroplasmonic assembly of gold nanoparticles and endonuclease H-paII the methyltransferase activity and inhibition has been studied [42]. Self-assembly technique has been used for the detection of ochratoxin A with the reported limit of detection as low as 0.15 pg/mL. In this experiment the construction of heterogeneous system with Au core and Ag satellites was created [43]. For the demonstration of the zeptamolar DNA detection the multimetal shell-

Recently an alternative sensing scheme was demonstrated on an example of the alpha-fetoprotein (AFP) detection. NP dimers were formed by AFP aptamer binding to its complementary sequence immobilized on gold nanoparticles and display strong chiroptical activity. The addition of AFP aptamer led to its strong binding to immobilized aptamers and to the destruction of the aptamer-DNA hybrid accompanied by the decrease of CD signal. The authors reported the detection limit as low as 11 pg mL−1. Since AFP is a marker of liver cancer, such

Similar approach was used for the detection of 8-hydroxy-2′-deoxyguanosine, a well-known biomarker for the oxidative DNA damage, in human serum [46]. CD intensity showed log-linear correlation with the concentration of the analyte

The same strategy has been applied for monitoring the intracellular concentration of analyte molecules. For instance, the detection of adenosine-5′-triphosphate

*Schematics of the Au-Ag heterodimer bridged by immunocomplex with prostate-specific antigen (PSA) (a); (b) the CD spectra for different concentrations of PSA; (c) the CD calibration curve for PSA detection as a function of logarithmic PSA concentrations. Reproduced with permission from Wu et al. [32], Copyright 2013* 

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

engineered assemblies had been used [44].

detection scheme is of high practical interest [45].

molecules, and the limit of the detection as 33 pM was reported.

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

*Smart Nanosystems for Biomedicine, Optoelectronics and Catalysis*

**nanoparticles**

field in the gap [31].

**3. Chiral molecules in the gap of dimers of plasmonic metal** 

A similar chirooptical phenomenon is theoretically predicted for chiral molecules located in the gap of dimers of plasmonic nanoparticles for both resonant and nonresonant CD signals [27–30]. Strongly amplified electric field localized in the gap of such nanostructures results in a strong CD amplification. The enhancement factors up to 3000 can be expected for 5 nm gap. **Figure 3a,b** demonstrate the schematic image of the system and the correlation of CD enhancement with electric

This effect was experimentally observed in several systems of aggregated metal nanoparticles (NP), such as spherical gold nanoparticles conjugated to oligonucleotides [32–34], cysteine-modified gold nanorods [35, 36] and nanospheres [37, 38], as well as cholate-coated silver nanoparticle [39], etc. The CD signal is greatly enhanced by particle agglomeration, which leads to the formation of nanometer-sized gaps. A demonstration of chiral biosensing based on the formation of asymmetric plasmon dimers has been reported recently [40]. The authors detected CD signal generated by self-assembly of gold nanorods using an antigen-antibody recognition reaction. The low detection limit for bisphenol A of 0.02 ng/mL was reached. To assemble nanoplasmon dimers with a tunable chiroptical response, the immobilization of highly specific complementary DNA primers on their surface were

*Chiral molecules in the gap of a plasmonic dimer: schematics (top), (a) calculated CD enhancement factor for different gap size; (b) corresponding values of average electric field in the gap volume. Reproduced with* 

**44**

**Figure 3.**

*permission from Nesterov et al. [31].*

fulfilled [34]. Using this method and its modifications, various analytes were successfully being detected. For instance, self-assembly of silver ions was carried out with a detection limit of 2 pM by inducing the nanodimer assembly reaction [41]. By triggering the DNA-based chiroplasmonic assembly of gold nanoparticles and endonuclease H-paII the methyltransferase activity and inhibition has been studied [42]. Self-assembly technique has been used for the detection of ochratoxin A with the reported limit of detection as low as 0.15 pg/mL. In this experiment the construction of heterogeneous system with Au core and Ag satellites was created [43]. For the demonstration of the zeptamolar DNA detection the multimetal shellengineered assemblies had been used [44].

Recently an alternative sensing scheme was demonstrated on an example of the alpha-fetoprotein (AFP) detection. NP dimers were formed by AFP aptamer binding to its complementary sequence immobilized on gold nanoparticles and display strong chiroptical activity. The addition of AFP aptamer led to its strong binding to immobilized aptamers and to the destruction of the aptamer-DNA hybrid accompanied by the decrease of CD signal. The authors reported the detection limit as low as 11 pg mL−1. Since AFP is a marker of liver cancer, such detection scheme is of high practical interest [45].

Similar approach was used for the detection of 8-hydroxy-2′-deoxyguanosine, a well-known biomarker for the oxidative DNA damage, in human serum [46]. CD intensity showed log-linear correlation with the concentration of the analyte molecules, and the limit of the detection as 33 pM was reported.

The same strategy has been applied for monitoring the intracellular concentration of analyte molecules. For instance, the detection of adenosine-5′-triphosphate

#### **Figure 4.**

*Schematics of the Au-Ag heterodimer bridged by immunocomplex with prostate-specific antigen (PSA) (a); (b) the CD spectra for different concentrations of PSA; (c) the CD calibration curve for PSA detection as a function of logarithmic PSA concentrations. Reproduced with permission from Wu et al. [32], Copyright 2013 American Chemical Society.*

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

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 sensitivity and selectivity in practical applications.
