Advances in xanthine biosensors and sensors: A review

Xanthine is derived from hypoxanthine by xanthine oxidase (XOD), a flavoprotein containing molybdenum and non-haem iron, sulfur and from guanine by guanine deaminase. Uric acid is produced as a result of xanthine oxidation by XOD. Xanthine is used as an indicator of fish freshness, based on the reactions in which ATP is degraded into xanthine and its quantity increases with time of fish death. In chemical nomenclature, xanthine is 3, 7-dihydro-purine-2, 6-dione. In animal tissue xanthine is derived from guanine and adenosine-3-phosphate [1] by catabolic reactions in body. These reactions lead to accumulation of xanthine in body, which causes death of organism. In xanthine metabolism sequence first ATP is hydrolyzed to ADP which is converted into inosine, hypoxanthine and xanthine as shown in Fig. 1. XOD catalyzes the oxidation of xanthine to uric acid.

Xanthine concentration increase may be a symptom of several physiological diseases like depressed purine salvage pathway, which leads to Lesch-Nyhan syndrome. Xanthinuria may develop due to decreased xanthine oxidase activity. Unrestrained xanthinuria leads to disease like stone formation in kidneys, muscle disease, urinary tract ailments. Xanthine is excreted 10 -times more swiftly than uric acid but its concentration is low in urine, because xanthine is changed into uric acid by XOD. Due to low solubility of xanthine, increase xanthine concentration can lead to renal calculus disease. The level of xanthine in human urine varies between 41 and 161 mM [2], [3]. Xanthine concentration in serum is 100 times lower than uric acid [4]. After death of organism, degradation of nucleotides to hypoxanthine and xanthine occurs. Techniques used in determining xanthine, provide information to assess quality & conditions required for storing meat products and, in pharmaceutical industries for making good variety of products. Traditional methods used for detecting xanthine are Biocentric voltammetry [5], Florescence spectroscopy [6], Microassay [7], Spectrophotometry [8] high pressure liquid chromatography (HPLC) [9], enzymatic fluorometry, fluorometric mass spectrometry fragmentography [10], capillary column gas chromatography [11], and enzymatic colorimetric [12].

Biosensors are indeed promising tools for measuring analytes accurately and quickly. They consist of a biological sensing component, which is capable of recognizing and binding to a specific analyte, and a transducer that converts the binding event into a measurable signal. Biosensors can be used for a wide range of applications, including clinical diagnosis, environmental monitoring, and food safety testing. As you mentioned, biosensors offer several advantages over traditional analytical methods, such as being low-cost, simple, sensitive, rapid, and selective [13]. They can also be made portable, allowing for point-of-care testing in remote or resource-limited settings. Professor Leland C Clark Jr. is indeed widely considered as the inventor of the biosensor. In the 1960 s, he developed the first enzyme-based biosensor, which used an oxygen electrode to detect glucose levels in blood samples. This ground breaking work paved the way for the development of modern biosensors and earned Clark numerous accolades, including the National Medal of Science in 1985. Since then, biosensors have evolved significantly, and a wide range of sensing components and transducers have been developed to target different analytes and applications. Ongoing research is focused on improving the sensitivity, selectivity, stability, and reproducibilityof biosensors, as well as integrating them with advanced data analysis and communication technologies for real-time monitoring anddecision-making.

Nanotechnology has indeed opened up new opportunities for the development of biosensors. Nanoparticles, carbon nanotubes, polymers, and other nanomaterials have unique properties that can be harnessed to enhance the performance of biosensors. Nanoparticles, for example, have high surface area-to-volume ratios, which increase their sensitivity to analytes. They can also be functionalized with specific recognition elements, such as antibodies or aptamers, to enhance their selectivity. Carbon nanotubes, on the other hand, have exceptional electrical properties that make them suitable for transducing biological binding events into measurable electrical signals. Polymers, including conductive and non-conductive ones, can be used as sensing materials or as matrices to immobilize sensing components and enhance their stability. By combining these nanomaterials with other components, such as enzymes, antibodies, or DNA probes, it is possible to create nanocomposites, nanolayers, and nanothreads/ribbons, nanohybrids, and nanoclusters that can improve the sensitivity, selectivity, and stability of biosensors. These approaches have been used for a wide range of applications, such as glucose monitoring, pathogen detection, and environmental monitoring. However, it is important to note that the use of nanomaterials in biosensors also raises concerns about their potential toxicity and environmental impact. Therefore, it is crucial to carefully evaluate the safety and regulatory aspects of these technologies as they continue to develop. The development of enzymatic and non-enzymatic electrochemical biosensors for the detection of xanthine is an area of active research.

Xanthine is a purine base that is present in many biological fluids and is a precursor to uric acid, which can accumulate in the body and cause health problems [14]. Enzymatic biosensors for xanthine detection typically use xanthine oxidase (XOD) to catalyze the oxidation of xanthine to uric acid, which can then be detected using an electrochemical transducer, such as a modified electrode. Non-enzymatic biosensors, on the other hand, rely on the direct electrochemical oxidation of xanthine at the surface of the modified electrode. Various modified electrodes have been developed for the detection of xanthine using both enzymatic and non-enzymatic approaches. Carbon-based electrodes, such as glassy carbon, carbon nanotubes, and graphene, have been widely used due to their high surface area and good electrical conductivity. Metal-based electrodes, such as gold, platinum, and silver, have also been used, as well as modified electrodes using metal oxides or conducting polymers. The modification of these electrodes with various materials, such as enzymes, nanoparticles, or organic or inorganic compounds, can improve their sensitivity, selectivity, and stability for xanthine detection. For example, XOD can be immobilized on the surface of the modified electrode using various techniques, such as physical adsorption, covalent attachment, or entrapment in a polymer matrix. Other approaches include the use of nanomaterials, such as metal nanoparticles, to enhance the electrochemical signal and improve the detection limit. Recent studies have reported the development of novel xanthine biosensors based on modified electrodes, including those using carbon nanotubes or graphene oxide, metal nanoparticles, or conducting polymers as sensing materials. These biosensors have shown promising results in terms of sensitivity, selectivity, and reproducibility, and have the potential to be used in clinical and research settings for the detection of xanthine [15]. Overall, the development of enzymatic and non-enzymatic electrochemical biosensors based on modified electrodes represents an important advancement in the field of xanthine detection and has potential applications in the diagnosis and monitoring of various health conditions.

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