**2. Healthcare applications of biosensors**

The main objective in promoting, presenting, and researching healthcare services is to assess the health status, detect the early and advanced stages of diseases, and monitor treatment progress through noninvasive methods. To achieve this goal, three essential conditions must be met: specific biomarkers to differentiate between normal and infected states, noninvasive monitoring approaches for these biomarkers, and techniques to identify and differentiate them. Early-stage detection is vital for patient's survival and favorable prognosis. This criticality necessitates the development of highly sensitive and specialized methods. The three diseases with the highest incidence, impact, prevalence, and mortality rate worldwide are diabetes, cardiac diseases, and cancer. Biosensors are rapidly emerging as crucial research areas, particularly for these three diseases. They provide advantages such as rapid response times, userfriendliness, affordability, and the ability to create simple and disposable devices suitable for mass production [1]. This section presents the latest research findings on the application of biosensors in diagnosing and treating diseases such as parasitic malaria, dementia, Alzheimer's, and infections, in addition to the mentioned diseases.

## **2.1 Biosensor applications for diabetes**

Diabetes mellitus (diabetes) is a chronic metabolic illness that harms the body because blood sugar levels are too high. The prevalence of type 2 diabetes, which is more prevalent in adults, has increased globally. On the other hand, type 1 diabetes affects a sizable proportion of the population and is linked to a high risk of mortality. Tragically, the frequency of the condition and the number of persons receiving diabetes diagnoses are both increasing [2]. Affordable medical care, including insulin, is crucial for diabetic individuals' survival. Regular glucose monitoring is essential, but current testing products often cause discomfort and dissatisfaction. The development of a reliable, noninvasive device or technique for the identification and treatment of diabetes is long overdue. Glucose sensors, which detect glucose levels in the subcutaneous fat, are now readily available as compact and minimally invasive devices [3]. Long-term stability, oxygen isolation, miniaturization, user-friendly operation, and biological compatibility are key characteristics of *in vivo* blood glucose sensors. The main requirement has been ensuring long-term biocompatibility, which restricts the usage of *in vivo* glucose sensors to short time periods. Sensor sensitivity is compromised by the migration of low molecular weight compounds across the outer membrane of the polymeric sensor. To address this issue, advances in microdialysis or ultrafiltration technology are employed in conjunction with glucose-detecting biosensors [4].

To monitor their blood glucose levels, diabetes patients rely on glucose test strips. However, existing test strips often suffer from cost and durability limitations. In response, scientists have created an electrical sensor constructed from paper that has been molecularly imprinted with glucose recognition sites. This sensor demonstrates good accuracy in detecting glucose concentrations in solutions derived from bovine blood, as indicated by its calibration graph. By addressing the shortcomings of traditional test strips, this nonenzymatic glucose biosensor has the potential to reduce medical expenses and enhance accessibility in underserved areas [5]. In a separate study, scientists have created a paper chip for glucose detection in saliva using a smartphone. This chip combines luminol-encapsulated metal–organic frameworks and glucose oxidase (GOx) on filter paper, exhibiting a color change from purple to brown in the presence of glucose. Leveraging the image processing capabilities of smartphones, this chip enables fast and accurate quantification of glucose, particularly benefiting individuals with color vision impairments. Its simple design, affordability, and compatibility with mobile devices make it a precise and user-friendly tool for evaluating glucose levels [6]. Another work used a three-dimensional (3D) porous graphene aerogel and glucose oxidase (GOx) to create an enzymatic electrochemical microfluidic biosensor. Excellent selectivity, stability, and a linear detection range of 1 mM to 18 mM (R2 : 0.991) were all displayed by the biosensor. This biosensor has a low limit of detection (LOD: 0.87 mM) and successfully monitors glucose levels in serum samples, which has tremendous promise for enhancing prevention of diabetes and clinical diagnosis [7]. For the detection of glucose and saccharides, a self-healing smart hydrogel sensor with boronate ester linkages has been created. The sensor demonstrates strong identification ability and a wide determination range for glucose by leveraging the optical capabilities of a photonic crystal and the regenerative qualities of the hydrogel. The self-healing feature of the sensor increases reliability while reducing the cost of the measurement procedure. The sensor has promise for early diabetes screening despite its weak selectivity for monosaccharides [8]. In 2021, the development of copper(I) halide and copper(II) oxide nanoparticles (CuBr@CuO

NPs) on Cu foils has revolutionized electrocatalytic glucose detection. This electrode has a low overpotential, a wide linear range, and remarkable electrocatalytic activity. Furthermore, a strong link between blood glucose levels has been confirmed by validation trials utilizing salivary samples. Because of this, the noninvasive glucose monitoring system using the NP-based electrode has tremendous potential for use by diabetic patients [9]. Salivary glucose levels in diabetics can be detected noninvasively with a toothbrush containing an amperometric biosensor. In a study by Liu et al., the sensor electrodes, made of carbon graphite and Ag/AgCl inks, demonstrated successful glucose detection within a concentration range of 0.18 mM to 5.22 mM in less than 5 minutes. This discovery holds intriguing possibilities for advancing healthcare and introducing innovative toothbrush sensors [10]. Particularly in the case of diabetes, early disease detection, ongoing monitoring, and rapid diagnosis are essential for individualized care. Visual inspection tests, low-cost analysis, and individualized home testing have all been transformed by portable biosensors made of nano/microscale materials. Salivary trace glucose can now be detected noninvasively using an extremely sensitive minisensor. Thanks to the strong electrocatalytic ability and electron transfer rate of the 3D nanostructured CuO nanoflake array, it exhibits exceptional sensitivity and resolution at low glucose concentrations [11]. This small sensor holds tremendous potential for noninvasive glucose monitoring in saliva for diabetic patients, offering a broad linear range, excellent sensitivity, LOD, and the ability to distinguish between people with diabetes and healthy individuals. Point-of-care (PoC) health services offer diagnostics and vaccinations in a sterile environment. PoC testing improves patient satisfaction and glucose control, benefiting diabetes management. Glucose sensors utilizing chitosan-capped ZnS-doped Mn nanoparticles provide fast and accurate detection. Among the tested materials, chitosan-capped ZnS-doped Mn at 1% weight demonstrates superior sensitivity, selectivity, and stability [12].
