**3. Platform with nanomaterials in the diagnosis of COVID-19: a brave new world**

Biosensors are analytical devices that incorporate a biological recognition element capable of detecting the presence, activity, or concentration of the sample under analysis connected to a transducer. This biological element can be a microorganism, an antibody, oligonucleotides, lectins, biomolecule enzymes that can

interact with the target substrate. About the transducer, it can be an electrode, fiber optic, or oscillating quartz [42, 44]. Thus, biosensors are one of the most popular types of point-of-care devices in various areas of diagnostics, which offer several advantages such as low cost, the capability of miniaturization, and high sensitivity and selectivity.

Immunosensors are analytical devices of the biosensor class, which detect and transmit information regarding biochemical changes involving integrating a biological element with an electronic interface [45, 46]. This integration can convert a biological signal into an electrical response that is proportional to the concentration of the analyte. Thus, these biosensors can recognize a specific antibody or antigen by forming an antigen–antibody immunocomplex. The recognition event is detected and converted, through a transducer, to a measurable signal (such as electrical current, for example). The primary transducers used in immunosensors are electrochemical, optical, and piezoelectric. Therefore, the incorporation of specific nanomaterial can be intensified by improving the biosensor's sensitivity and versatility.

Genosensors can also be used, a specific type of biosensor based on nucleic acid chemistry phenomena, such as the hybridization process [47]. Nucleic acids have been widely used in the development of biosensors for drug detection, identification of pathogenic microorganisms and other biological substances, and the diagnosis of diseases. The sensory technique through hybridization involves the immobilization of an oligonucleotide probe on the surface of a transducer and subsequent sensor exposure to a sample containing the complementary sequence (target oligonucleotide) with consequent hybridization. Complementary DNA (cDNA) is a DNA synthesized from a messenger RNA molecule in a reaction catalyzed by the enzyme reverse transcriptase. Thus, the incorporation of nanomaterials on the biosensor's surface ensures the enhancement of the electrochemical response.

Our group has been demonstrating through publications and patents expertise in the development of nanomaterials with specific properties, such as increased sensitivity of some devices, biocompatibility, and low genotoxicity, essential properties in developing nanotechnological platforms [48–53]. Toxicity is an important parameter in nanomaterials, but depending on synthesis methodologies it is possible to decrease toxicity. For example, Silva et al. demonstrated some toxicities of nanomaterials, some influenced by the crystalline phase, composition or type of material [54–61]. In relation to quantum dots, synthesis methodologies were developed, making it possible to increase cellular viability and specificity aiming at several applicability as biological probes [52, 53, 62–68].

The development of artificial intelligence software enables more accurate detection and quantification and low-cost analytical platforms [69, 70]. These nanotechnological platform [71] s can be used in large-scale production, with low cost and low consumption of samples and reagents [6, 72].

High-quality, low-cost nanotechnological platforms based on the detection of anti-SARS-CoV-2 antibodies may be the key to defining groups already exposed to the disease, even if asymptomatic, that have a potentially protective immune response, a crucial factor for delimitation priority immunization groups. Besides, we can determine the loss of protective immune response after an episode of COVID-19, which leads to a possible chance of reinfection. Some advantages are the amount of sample of interest, in the order of μL, simultaneous analysis of several analytes in the same device and miniaturization, being portable, light, and easy to use the equipment. Also, nanotechnological platforms can be used to assess and monitor the success of immunization strategies, which should soon begin to be administered on a large scale, and the extent and duration of their protection will need to be determined.

#### *Sensor Surface Design with NanoMaterials: A New Platform in the Diagnosis of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.97056*

Several diagnostic methods have been reported, aiming at biomedical applications, especially in the diagnosis of covid-19, to detect the coronavirus in clinical, research, and public health laboratories. Based on biosensors for SARS-CoV-2, diagnostic methods presented have analytical performance and response times ranging from a few minutes to several hours, which make them promise for practical use in health care points, showing as a strong ally for control of endemics and pandemics.

An overview of current efforts to improve point-of-care diagnostic systems based on biosensors using different nanomaterials at COVID-19 is presented in **Table 2**.

Currently, diverse electrochemical biosensors have been lately developed for the detection of the SARS-CoV-2 using modified electrodes with metallic nanoparticle or nano-islands or nanostars, carbon nanofiber (CNF), using inorganic quantum dots, zinc oxide nanowires (ZnO NWs) or nanorods, bimetallic nanoparticles, Graphene Oxide (GO) nanosheet and other modifications show in **Table 2**. These nanomaterials showed excellent applications in biosensors because of their ease of functionalization, large surface area, stability, on the stable immobilization of probe molecules, the blocking reagent to minimize nonspecific binding, high electronic conductivity (accelerate the electron transfer), high carrier/charge mobility, and strong adsorption capability that increase the sensitivity of electrochemical platform due to their excellent unmatched properties followed by enhancement in the electrochemical response toward the selective detection of SARS-CoV-2.

Vadlamani, B S. et al., the synthesis of a TiO2 functionalized with cobalt but susceptible electrochemical sensor based on nanotubes (Co-TNTs) for rapid detection of SARS-CoV-2 using peak detection (binding domain receptor (RBD)) present on the virus surface [83]. A simple, low-cost, one-step electrochemical anodization route was used to synthesize TNTs, followed by an incipient wetting method for cobalt functionalization of the TNT platform, which was connected to a potentiostat for data collection. This sensor specifically detected the S-RBD protein from SARS-CoV-2, even at very low concentrations (range 14 to 1400 nM (nanomolar)). Besides, our sensor showed a linear response in the detection of viral protein in the concentration range. Thus, our Co-TNT sensor is highly effective in detecting the SARS-CoV-2 S-RBD protein in approximately 30s.

Cuy and Zhou, 2019, showed in their review work that timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research [86]. In this review, biomarkers/indicators for diagnosis of coronavirus 2019 disease or detection of severe acute respiratory syndrome coronavirus 2 in the environment are summarized and discussed. However, antibody detection methods can be combined with real-time quantitative polymerase reverse transcriptase chain reaction to improve diagnostic sensitivity and specificity and boost vaccine research significantly. The deep throat saliva and induced sputum are desired for the RT-qPCR test or other early detection technologies. The ultra-sensitive and specific laboratory diagnostic method and portable devices are essential to control the rapidly evolving COVID-19 pandemic associated with SARS-CoV-2. Currently, computed tomography, RT-qPCR, and LFICS based on the colloid Au NPs (colloidal gold method) have been developed.

Based on the table results, we can verify that the biosensors that showed the best sensitivities are using carbon-based materials due to their conductive properties, metallic oxides (ZnO and TiO2) with supercapacitor properties, and nanocomposites (containing the capacitive and metallic systems).

In nanomaterials, the effects of size, morphology, and chemical structures have a strong influence on the optical, electrical, and magnetic properties. Thus, the tuning of these parameters allows maintaining the same material and intensifying the biosensors' responses. Another critical parameter is the synergism between


#### *Biotechnology to Combat COVID-19*


**Table 2.**

*Comparison of electrochemical biosensors for the detection of (SARS)-CoV-2.*

#### *Sensor Surface Design with NanoMaterials: A New Platform in the Diagnosis of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.97056*

nanomaterials, several biosensors using more than one type of nanomaterials to further improve sensitivity. Thus, unfortunately, this systematic study of the literature in biosensors does not exist, being difficult to compare the sensitivity properties using different materials and nanocomposites.
