*Applications of Cutting-Edge Biosensors in Healthcare and Biomedical Research DOI: http://dx.doi.org/10.5772/intechopen.112693*

range is broad (10 fM to 100 nM). Its successful use in serum samples from healthy people and people with coronary heart disease demonstrates that it is accurate compared to qRT-PCR. This biosensor has excellent potential for the detection of exosomal miRNA in cardiovascular illness due to its long-term stability, sensitivity, usability, and cost-effectiveness [14]. In a recent study, scientists created an aptasensor with a LOD of 0.01 ng/mL that can measure troponin T (TnT) levels and diagnose myocardial infarction at an early stage. By assisting in the prevention of myocardial infarction-related mortality and the decline in the prevalence of patients with cardiac failure, this aptamer-based biosensor has the potential to have a large positive effect on healthcare. The broad use of this biosensor may also save money, speed up diagnoses, and increase the ability to identify TnT for myocardial infarction [15]. In the face of the 2019 coronavirus disease, timely detection and treatment of cardiovascular disease remain imperative for improving survival rates. To meet the growing demand for round-the-clock vital sign monitoring, healthcare providers have turned to wearable devices equipped with vital sign sensors as a vital solution. However, previous technologies faced significant challenges, primarily due to high power consumption. This sensor captures essential vital indicators such as blood sugar, pulse, and oxygen levels, all while consuming minimal power. Its lightweight and compact design allows for seamless integration into flexible wristbands. By monitoring the subtle movements of the radial artery, this sensor provides accurate and continuous noninvasive measurements. The implications of this technology are far-reaching, holding tremendous promise for integrating telehealth into our daily lives and advancing the field of wearable technology [16].

#### **2.3 Biosensor applications for cancer**

Many low- and middle-income nations lack the resources needed to adequately manage this cost, which prevents numerous cancer patients worldwide from having adequate access to prompt and effective treatment and diagnosis. Cancer testing with biosensors offers helpful and profitable procedures. Compared to microarray or proteome analysis, it is more rapid, simpler to use, more affordable, and less technically complex. Still, additional technological developments are needed for protein-based biosensors. Multiple marker analysis by multi-array sensors would improve the diagnosis of cancer. To detect biomarkers, antibodies are frequently used as molecular recognition molecules. There have been numerous successful biosensor studies for cancer diagnosis, one of which utilized an ultrasensitive DNA electrochemical biosensor. This biosensor employed a carbon paste electrode amplified with ZIF-8 and 1-butyl-3-methylimidazolium methanesulfonate to detect the anticancer drug mitoxantrone in aqueous solutions. By exploiting the interaction between mitoxantrone and guanine bases of ds-DNA, as confirmed through docking research, the biosensor exhibited robust catalytic effects and precise determination capabilities. With a LOD of 3.0 nM, it successfully detected mitoxantrone across a wide concentration range of 8.0 nM to 110 M. Furthermore, the biosensor demonstrated excellent recovery results for detecting mitoxantrone in injectable samples [17]. Pharmacological investigations have brought attention to viscumin, a plant-derived protein with potential applications in cancer treatment. In a recent study, scientists utilized a 9-mer peptide sequence as a template to create a molecularly imprinted polymer. Under the influence of ultraviolet light, the functional monomer formed hydrogen bonds with the epitope, resulting in the polymer's structure. Subsequently, the epitope was extracted from the polymer surface using a solution of acetic acid

and sodium dodecyl sulfate (SDS). When evaluated in blood plasma and urine, the nano-biosensor exhibited selectivity [18].

It would be ideal to apply self-powered biosensors to the delivery of pharmaceuticals. In related work, a targeted medication delivery system and a glucose-O2 fuel cell-based biosensor were successfully combined. This resulted in a small, selfsustaining drug delivery model with self-diagnosis and evaluation capabilities. The biosensor also functions as a component of evaluation, tracking the effectiveness of treatment by examining drug-induced apoptosis cells in therapeutic cancer therapy [19]. In a recent work, utilizing methotrexate (MTX) as a model system, an analytical method for detecting an anticancer treatment in whole blood was developed. In order to facilitate redox cycling, the electrode surface of the biosensor used a unique modified carbon nanotube. Due to the cooperative action of the nitrogen-CNT, this composite displayed excellent electrical conductivity and catalytic activity. With low LOD (45 nM), a broad detection range (0.01–540 M), excellent selectivity, and longterm stability for MTX detection, the modified screen-printed electrodes (SPE) with WP/N-CNT demonstrated impressive performance, making it ideal for efficient and mobile MTX detecting, even in blood samples [20].

#### **2.4 Biosensor applications for Parkinson's disease**

Parkinson's disease (PD) is a degenerative brain condition that causes a variety of nonmotor difficulties, including cognitive decline, mental disorders, sleep disturbances, and sensory disturbances, in addition to motor symptoms like slow activity, shaking hands, strength, and difficulties with balance. Communication, activity, and general well-being of life are all further negatively affected by motor dysfunctions including muscular weakness and spasms. Because of their gradual nature, these signs frequently result in limitations and rising healthcare costs. Biosensors technical advancements open up new diagnostic approaches for PD with the use of a novel platform that enables accurate, reliable, and versatile identification to be achieved with little trouble and discomfort for patients. A rapid and precise miRNA biosensor was developed using the target-triggered three-way junction (3-WJ), terminal deoxynucleotide transferase (TDT)/Nt.BspQI, and activated copper nanoparticles (Cu NPs). The biosensor successfully detected target miRNAs down to a minimal detection limit of 1 fM at 1.75 h [21]. By examining whole blood RNA samples from patients with Parkinson's disease, its applicability was proven. Additionally, a label-free liquid crystal biosensor based on DNA aptamer was created for sensitive alpha-synuclein detection, enabling early Parkinson's disease diagnosis and offering a flexible detection platform [22]. Alpha-synuclein can be detected in serum samples using a surface plasmon resonance (SPR) biosensor that has been created utilizing magnetite nanoparticles (Fe3O4 NPs) and matched antibodies. The sensitivity of the SPR is greatly improved by depositing Fe3O4 NPs on the surface of Au at a high density, enabling a detection limit of 5.6 fg mL−1, 20.000-fold lower than commercial Enzyme-linked immunosorbent assay (ELISA). A highly sensitive and specific method for the early diagnosis of Parkinson's disease was proven using the SPR sensor, which allowed for the accurate quantification of -syn in diluted serum samples [23]. In another study, Sonuç et al. developed a highly sensitive electrochemical neurobiosensor by utilizing an electrode doped with a nanocomposite of multiwalled carbon nanotubes (MWCNT) and gold nanoparticles (AuNP). This nanostructurebased electrode was employed to detect DJ-1, a protein responsible for mitigating oxidative stress and managing mitochondrial dysfunction in Parkinson's disease.

## *Applications of Cutting-Edge Biosensors in Healthcare and Biomedical Research DOI: http://dx.doi.org/10.5772/intechopen.112693*

The neurobiosensor showed a LOD of 0.5 fg mL−1 and range of 4.7–4700 fg mL−1. With its ability for selective determination, the biosensor shows potential for identifying DJ-1 protein in cerebrospinal fluid (CSF) and saliva [24]. In 2022, Fan et al. developed a minimally invasive biosensor based on a flexible differential microneedle array (FDMA) to accurately monitor the dynamic concentration of levodopa (L-Dopa) in PD patients and lower the risk of consequences. The FDMA biosensor, which has two functional electrodes, has great anti-interference performance when it comes to separating out interfering chemicals from L-Dopa. A viable solution for continuous and less invasive monitoring of L-Dopa levels in PD patients, the biosensor shows a wide linear dynamic range, good sensitivity, and long-term stability [25]. Anthocyanins, pigments known as flavonoid present in fruits and vegetables, were studied for their effects on amyloid fibrils linked to neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Using total-internal-reflection-fluorescence microscopy (TIRFM), they were able to directly observe how anthocyanins broke down amyloid beta (Abeta) fibrils. The findings showed that the number of hydroxyl groups in the anthocyanin's six-membered ring B determines the disassembly activity of Abeta fibrils, with delphinidin-3-galactoside having the maximum disassembling activity. This study emphasizes the significance of hydroxyl groups and shows how TIRFM-QCM can be used to investigate chemical interactions with amyloid fibrils [26].

## **2.5 Biosensory applications for Alzheimer's**

Dementia is a collection of brain disorders causing progressive and severe loss of cerebral disorders, including memory, thinking, behavior, and emotions. It can affect anyone regardless of social class, gender, ethnicity, or location, with a higher prevalence among older individuals.

With the developing R&D studies, researchers developed a surface plasmon resonance imaging (SPRi)-based biosensor to evaluate extracellular vesicles (EVs) in plasma samples from Alzheimer's disease (AD) patients and normal individuals, successfully identifying and identifying EV populations formed by various cell types. The quantity and particular traits of the EV populations were significantly different in AD patients and healthy controls, according to comparisons between their EV profiles [27]. For the development of specific therapy approaches, the noninvasive early detection of AD biomarkers is vital. For this reason, Researchers have successfully developed highly flexible nanopillar-based electrochemical biosensors with a significantly large surface area by depositing gold on a polyurethane substrate. The biosensors were made biocompatible through the utilization of a self-assembled monolayer of thiol chemistry, enabling the effective immobilization of antibodies. Notably, these biosensors exhibited exceptional electrochemical performance, demonstrating consistent and reliable detection of beta-amyloid with a sensitivity of 0.14 ng mL−1 and outstanding repeatability. These findings highlight the tremendous potential of the nanopillar-based immunoelectrochemical biosensor as a robust and promising platform for point-of-care diagnostics [28].

#### **2.6 Biosensor applications for various diseases**

Biosensor development for diagnosing various diseases, including COVID-19, coronary artery disease, diabetes, cancer, dementia, Parkinson's disease, malaria, and infection, is the focus of extensive research (coronary artery disease, diabetes, cancer, dementia, Parkinson's disease have already been discussed earlier in this text). The urgency for rapid and affordable diagnostics is particularly evident in the case of COVID-19, where identifying asymptomatic individuals and curbing local transmission is crucial. One study proposes the use of cholesteric liquid crystal biosensor platforms as a one-step, wash-free, and rapid detection method for the SARS-CoV-2 virus, considering the limitations of antibody-based serological tests. Cholesteric liquid crystals have the potential to revolutionize healthcare by providing efficient and rapid diagnostic capabilities for various disorders [29]. For the purpose of diagnosing SARS-CoV-2, a quick, inexpensive, and reliable paper-based electrochemical sensor chip has been created. Using gold nanoparticles (AuNPs) coated with certain antisense oligonucleotides (ssDNA), the sensor specifically targets the viral nucleocapsid phosphoprotein. These probes can be read with a handheld device and are immobilized on a paper-based electrochemical substrate. The SARS-CoV-2 RNA may be detected by the biosensor with a LOD of 6.9 copies mL−1 without the need for amplification, and findings are available in 5 minutes. Its capability to accurately identify between positive and negative samples with approximately 100% accuracy, sensitivity, and specificity was proven in clinical testing on COVID-19-positive patients and healthy individuals [30]. A highly sensitive biosensor for sensing SARS-CoV-2 has been developed using CRISPR-Cas12a technology. This biosensor utilizes the disaggregation of gold nanoparticles and resulting color changes caused by the degradation of single-stranded DNA triggered by SARS-CoV-2 nucleic acids. The color change can be easily observed by the naked eye or using a smartphone with a Color Picker App. The biosensor demonstrated excellent sensitivity, detecting as low as 1 copy muL−1 of SARS-CoV-2 without any interference from other substances. It successfully detected the SARS-CoV-2 gene in synthetic vectors, SARS-CoV pseudoviruses, and RNA without cross-reactivity [31]. For rapid SARS-CoV-2 detection in saliva, a label-free biosensor has been created. It utilizes a brand-new chemical formulation and reusable electrochemical sensor chips. The sensor has a short response time of 5 minutes and gives a quantitative measurement of viral load. With a LOD of 200 pM and 500 pM, respectively, it can find the virus in both phosphate buffer saline and human saliva. A COVID-19 pseudovirus has been successfully found using the sensor in an electrolyte solution. Overall, it demonstrates potential as a practical and reliable approach for identifying and tracking COVID-19 [32]. In a study by Xiao et al., an antibody chip biosensor is introduced as a rapid and automated method for detecting antibiotic residues in milk and pork. The biosensor immobilizes particular antibiotic conjugates on disposable chips using 3D polymer slides. Monoclonal antibodies and a fluorescencebased detection device enable the simultaneous detection of various antibiotics. With detection limits that are below maximum residue limits, the biosensor exhibits great sensitivity. The approach exhibits good precision and accuracy and requires little sample preparation. This biosensor provides an important quality control method for identifying antibiotic residues in food generated from animals [33]. Growing public health concerns include drug trafficking, particularly at ports, airports, and border crossing points. Detecting trace amounts of small drug residues presents a challenge. However, through the innovative use of fluorescently labeled antibodies and a monolithic affinity column, a highly sensitive immunosensor has been developed to address this issue. It takes less than 3 minutes to complete the assay and can detect cocaine at a limit of 23 pM within 90 seconds. The sensor may also detect as little as 300 pg. of cocaine using surface wipe sampling. One of the quickest and most accurate cocaine detectors available is this immunosensor, which provides measurement that is nearly continuous [34].
