Nanostructures in Biosensors: Development and Applications

*Gizem Karabulut, Nuray Beköz Üllen and Selcan Karakuş*

### **Abstract**

In recent years, there has been significant interest in advanced nanobiosensor technologies with their exceptional properties for real-time monitoring, ultrasensing, and rapid detection. With relevant experimental data, highly selective and hypersensitive detection of various analytes is possible using biosensors based on nanostructures. In particular, biosensors focus on vital issues such as disease early diagnosis and treatment, risk assessment of quality biomarkers, food-water quality control, and food safety. In the literature, there has been great attention to the preparation and sensing behavior of several nanomaterials-based sensors, such as polymer frameworks, metal-organic frameworks, one-dimensional (1D) nanomaterials, two-dimensional (2D) nanomaterials, and MXenes-based sensors. This chapter gives points to all aspects of fabrication, characterization, mechanisms, and applications of nanostructures-based biosensors. Finally, some smart advanced sensing systems for ultra-sensing nanoplatforms, as well as a comprehensive understanding of the sensor performances, current limitations, and future outlook of next-generation sensing materials, are highlighted.

**Keywords:** biosensor, nanostructures, sensing nanoplatform

### **1. Introduction**

Today, as a result of rapid industrialization, global problems bring about pollution, diseases, and many other problems. Early detection, prevention, and elimination of these problems have become very important for the continuity of the ecological system. Due to increasing technological developments, the rapid, precise, high-sensitivity, and reusable detection of these situations is made possible with biosensors. Biosensors are innovative, effective, and independent analytical devices that respond selectively and reversibly depending on the concentration or activity of the analyte to be determined in the sample [1–3]. With a brief historical overview of biosensors from past to present, in 1962, the first electrochemical enzymatic biosensor was invented by Clark et al. to detect glucose in biological samples due to the oxygenation of blood samples by reducing oxygen on the surface of the platinum electrode [1]. With this discovery, Leland C. Clark is referred to as the "father of the biosensor." In 1962, Clark determined the concentration of glucose by immobilization of the glucose oxidase on the surface of the amperometric enzyme electrode. In 1962, Montalvo and Guilbault reported the first potentiometric urease enzyme

sensor for the detection of the ammonium ion activity due to the enzyme-catalyzed hydrolysis [4]. Another fascinating work was presented by Opitz and Lubbers with the development of the optical biosensor for the detection of alcohol in 1975, which made the field of sensors very remarkable and rapid developments in this area continued [5]. One year later, Clemens et al. developed an electrochemical glucose biosensor for a bedside type of artificial bedside pancreas as a prominent work in the field of biotechnology [6]. At the beginning of the twentieth century, researchers at the University of Cambridge found a pen-sized detector for monitoring blood sugar levels [5]. In the light of ongoing research, different biosensors have been developed by integrating nanostructures for the selective detection of specific analytes. When biosensors were applied to pesticide determination, Ivanov et al. [7] emphasized that an enzymatic layer makes it difficult to operate the biosensor in real samples, especially in field conditions, and reduces the sensitivity and reproducibility of the results obtained. With this approach, they experimentally demonstrated the importance of producing new low-cost disposable pesticide biosensors in which the ultrathin film of the enzyme is directly immobilized to the surface. As a result of rapidly developing technologies in the last 20 years, Chinnappan et al. [8] proposed as an alternative to existing allergen detection methods. It was shown that graphene oxide (GO)-based biosensors for the detection of major shrimp allergens (tropomyosin) with affinity (30 nM) and LOD (2 nM) values in the low nanomolar range were highly sensitive when compared with traditional sensors. For an example of work on the detection of bacterial pathogens originating from water, Yaghoobi et al. [9] demonstrated the successful usage of the green selective, sensitive, stable, repeatable, and reproducible electrochemical biosensor in *Streptococcus Pneumoniae bacteria* with a low limit of detection (0.0022 ng/ml ~ 622 bacteria) and a high sensitivity (3432.9 Ω (ng/ml)−1). A glassy carbon electrode (GCE) was modified with DNA-lead nanoparticles (Pb NPs) for sensitive and selective detection of the bacteria. In a study on biosensors for early detection of cancer, Alves et al. (2022) developed a novel electrochemical biosensor for monitoring of breast cancer by immobilizing the biotin-C3 and biotin-H2 peptides in the screen-printed electrodes/poly 3-(3-aminophenyl) propionic acid/ avidin system [10]. As we advanced deeper into the pandemic, we saw the need for advanced sensor technologies as a solution in the public health response to COVID-19. As it is known, since December 2019, humanity has been going through a historical process related to the coronavirus [COVID-19]. The urgency of developing a fast, easily accessible, and highly sensitive biosensor to monitor COVID-19 in all countries has emerged. In particular, the importance of developing and researching biosensors that do not give false-negative results for viruses that are at risk of rapid transmission and have lethal effects, which is another problem for humanity, has been understood. Dai et al. reported the development of a novel COVID-19 biosensor highly-sensitive and rapid enzymatic detection of the COVID-19 spike antigen without sample labeling for the accurate and rapid diagnosis of SARS-CoV-2 infection [11]. In this study, the anti-SARS-CoV-2 spike monoclonal antibodies were immobilized onto the surface of biosensor for the specific recognition of the SARS-CoV-2 spike antigen. Thus, it has been proven by rapid development and successful experimental results that biosensors have a wide range of applications such as environmental applications, drug delivery, diagnostics, biomedicine, food quality and safety [12].

In particular, biosensors have a wide range of applications, such as environmental applications, drug delivery, diagnostics, biomedicine, food quality and safety, etc. [12]. The global biosensor market was valued at \$15.5 billion in 2015, but it was expected to grow to \$24.9 billion by 2021 [13]. In other words, it has shown an

#### *Nanostructures in Biosensors: Development and Applications DOI: http://dx.doi.org/10.5772/intechopen.108508*

increase of 60.6% in 6 years, an indication that it has a widespread usage network day by day. A biosensor is a compact device containing a biological or biomimetic sensing element. It consists of bioreceptor, electronic system, and transducer component [14]. The target analytes are the structures to be detected in the sample. Bioreceptors are structures that produce a measurable signal as a result of physicochemical changes that occur through interaction with the analyte as a result of physical or chemical bonding. These can be enzymes, nucleic acids (DNA or RNA), antibodies, tissues, aptamers, organelles, etc. [2, 12, 15]. After analyte and bioreceptor interaction, a number of physicochemical changes may occur, such as pH change, mass change, electron transfer, heat transfer, etc. [16]. When a physicochemical signal such as specific temperature, sound, light, weight or pressure is produced by the interaction of the bioreceptor with the analyte, the transducer converts it into a readable or measurable electrical signal [17]. Generally, biosensors can be classified according to the type of biorecognition element and transducer [18, 19]. Based on the biorecognition element, biosensors can be classified as antibody, enzyme, antigen, or oligonucleotide-based biosensors. Based on the transducer, biosensors can be classified as optical, electrochemical, magnetic, amperometric, potentiometric, piezoelectric, acoustic, or thermometric-based biosensors. In **Figure 1**, the schematic diagram of the classification and application areas of biosensors was presented. With the unique sensing performance of nanostructure-based biosensors, a variety of chemical and biosensing nanoplatforms have been reported.

In sensor applications needing continuous monitoring of many analytes, e.g., pesticides, drugs, heavy metals, and bacteria residues detection in real samples, volatile organic compounds (VCOs), biomarkers, specific allergens detection in blood, glucose have been investigated [16]. As known, biosensors are under the influence of more than one scientific area and require a multidisciplinary study. Therefore, it is a very suitable area for development. Recently, developments in nanotechnology and, accordingly, nanotechnological applications of biosensors have attracted attention in the scientific world. In general, the impact of nanotechnology and nanomaterials on the development of biosensors, recent innovations in this area, and future expectations are reviewed in this chapter.
