**4. The use of quantum dots in electrodes**

Electrochemical immunological sensors are strong candidates to be used as platforms in medical centers due to their great sensitivity and specificity associated with diagnostic tests. To increase these values, it is necessary to use signal amplification strategies in response to the analyte, mainly in immunosensors aimed at rapid detection [35].

The number of publications using QDs in electrosensors has increased exponentially since 2005. In addition, several publications relating nanoparticles of this type to modifications for the construction of immunosensors, comparisons of this material with bulky materials, immobilization platforms, and changes in electrodes and electrocatalysts were made during this period [35].

Quantum dots have been used in several signal amplification strategies to increase sensitivity in immunological electrochemical sensors due to their high surface-volume ratio. In addition to their biocompatibility when associating with other molecules, their unique reaction characteristics and surface modification capacity make this nanomaterial essential in these applications [35, 36].

QDs can also be used for marking various antibodies through conjugation methods involving the activation of esters through avidin-biotin-type bonds, among others. In addition, the electrodes can be directly modified with this nanomaterial and successively joined to molecules such as aptamers, antibodies, or antigens to recognize a specific target, where after the reaction, there will be a change in the electrochemical behavior [27, 37].

When electrodes are modified with nanostructures such as QDs, several functional groups allow greater accessibility of molecules, such as adsorption-type binding events, which occur on the surface of this electrode. In sequence, a fast electronic transfer is made due to the high conductivity of the material, in addition to the increase in the number of surface molecules associated with high surface area [38].

#### *Electro Sensors Based on Quantum Dots and Their Applications in Diagnostic Medicine DOI: http://dx.doi.org/10.5772/intechopen.111920*

One of the most used techniques when working with metallic nanoparticles involves the use of acidic solutions capable of dissociating metallic cations so that it is possible to quantify the bound nanoparticles through voltammetric and amperometric techniques, to measure the number of ions, which are proportional to the number of nanoparticles and in turn of the analyte [35].

Nanoparticles can also function as carriers of electroactive species and be measured. As these nanoparticles would create two distinct electrochemical signals compared to single-metal nanoparticles such as AuNPs or AgNPs, they can be loaded with species of diverse chemical composition, allowing their use in multiplexed electro sensors [39].

As the immobilized layer, which normally connects the nanoparticles to the electrode, prevents the substances from reaching its surface, the electronic transfer reactions are attenuated, with a low current background. However, due to the photoactivation capacity of the QDs, the condition changes drastically after the correct excitation of the light spectrum and redox reactions become possible, creating easyto-use, accessible, and portable sensor systems [40].

A common problem of the strategy that involves immobilizing the QDs on the electrodes is the production of unstable photocurrent (drift). One of the main reasons associated with this, including the poor connection between the QD-electrode, which ends up releasing the nanoparticles previously immobilized during the measurement of currents. In this case, coupling reagents capable of covalently joining the nanoparticles to the surface of the electrodes are used to guarantee the generation of stable photocurrents through the electronic conduction between both [41–43].

Another area for improvement in the direct connection of the QD-electrode is the so-called photo corrosion of the excited nanoparticles. In this case, the drift occurs because the QDs can act as capacitors; if, during the reduction and oxidation events of the system, there are no electron donors or acceptors in the solution, the nanoparticles are continuously reduced and oxidized by the electrode, generating a change in the photocurrent with the variation of time, affecting the stability of the reaction [44–46].

The incorporation of other nanoparticles into the electrode system along with QDs is an incredibly valuable approach to facilitate electronic transfer within the system. This alternative often involves the use of nanoparticles such as gold nanoparticles, carbon nanotubes, titanium dioxide, and graphene, which aid in enhancing the performance and efficiency of the QD-based electrol system. In addition to more, the use of these nanoparticles in the system helps to avoid charge recombination of the electronic carriers, ensuring greater sensitivity for the detection of redox species in the solution [47–50].

An alternative for modifying the electrode is the coating of ligands on the surface of the QDs for coupling to the electrode. In addition to these ligands adjusting the electrical properties, they make possible covalent and non-covalent connections depending on the strategy and the use of overlapping layers with the advantage of increasing the photocurrent magnitude [27, 51–53].

Generally, after light excitation and application of a specific potential, the electrons can tunnel from the electrode to the valence band of the QDs (**Figure 2**). Consequently, the conduction band's electrons interact with the solution's external electron acceptor molecules. In this case, the current increases proportionally with the concentration of acceptors on the surface. On the other hand, if the substances in the solution are electron donors, tunneling occurs in the opposite direction [54].

**Figure 2.**

*Electron transfer process at a quantum dot-modified electrode after illumination: (A) reduction process generated by the electron acceptor and (B) oxidation process generated by the electron donor.*

By comparing electrodes modified with QDs to unmodified electrodes, it becomes evident that the inclusion of nanoparticles offers an additional tool to regulate the reaction. The incidence of light directed to only a specific area allows the analysis of multiple regions within the same electrode. The analyte is only detected after the presence of light excitation. In this case, the resolution varies according to the acceptor molecule and the light system used, the name given to the strategy refers to the concept of light-addressable sensor systems [55–57].

When comparing theoretical and experimental models, it is possible to observe that both cite the implications associated with variations in the distance between the valence and conduction bands. The final formation of photocurrent is influenced by various factors, including the size of the nanoparticle, the distances between the electrode and the QDs, as well as the type of conductive properties of their ligands, the concentration of redox materials, and the light spectra. Thses parameters play crucial roles in determining the efficiency and characteristics of the generated photocurrent [41, 58, 59].

Another interesting concept of the QD-electrode system is its ability to recognize analytes without the need for labeling them with other secondary structures containing electroactive species. In this case, elements such as antibodies, aptamers, or DNA will be added on the surface of this, and only with the specific recognition of an analyte the charge of the system will be altered, characterizing the binding [60].

In addition to their role in coating the electrode surface, QDs can also serve as markers for molecules. They serve as electroactive structures that can be detected when the capture structure and the labeled analyte come into proximity, establishing a connection with the electrode. This system can also be amplified by increasing the number of molecules attached to the surface of nanoparticles [61].

Among the various ways of using QDs, electrochemiluminescence can detect a wide range of analytes in the solution. In this case, electrochemical reactions excite the nanoparticles, causing them to emit a certain fluorescence, which will be quantified concerning the amount of analyte recognized in the system [27].

Like many semiconductors, QDs can be excited through various means, including light spectra as well as chemical and electrochemical reactions. The emission of light from QDs can be controlled by applying potentials to the electrode, leading to sequential responses. One significant advantage of this approach is the ability to confine the reaction to a specific area without the need for external light sources. Additionally, the absence of a background associated with ambient light further enhances the precision and accuracy of the measurement conducted using QDs [62, 63].

#### *Electro Sensors Based on Quantum Dots and Their Applications in Diagnostic Medicine DOI: http://dx.doi.org/10.5772/intechopen.111920*

Similar to the photoluminescence, the physical properties of QDs, such as the distance between the valence and conduction bands and the change in the applied electrochemical potential, can also be explored to refine the final result system. This capability allows for the utilization of QDs in a multiplexed format, enabling their application in several new fields [64, 65].

Despite the various advantages of electrochemiluminescence with QDs, when compared to substances such as luminol, the yield is much lower, for this some strategies are used, such as modifying the electrode with graphene, carbon nanotubes, and titanium oxide, in addition to the use of nanoparticles of gold to amplify the luminescent signal of the system [66–68].

Another limiting factor of systems using electrochemiluminescence involves light emission in visible spectra, requiring protection against external input of wavelengths [69, 70].
