## 1 Introduction  
Microfluidics is the most advanced field of modern science and technology, due to a wide range of applications in different fields, such as medicine, biology, chemistry, or environmental protection [1, 2, 3]. The manipulation with a small amount of fluid is done in a microchannel network and integrated operations such as sample pretreatment, reagent storage, cell separation, mixing, and fluid separation along with micromechanical, optical, and electronic components for analysis and detection. It has the potential to integrate complex systems (Lab-on-Chip) in a miniaturized state by controlling the flow rate, providing a dynamic environment, conducting experiments in parallel, and monitoring analytes at a cellular scale [4, 5, 6] as non-invasive sample saliva becomes an important fluid for microfluidic and sensing applications due to a lot of information that describes dental and general health. The use of salivary samples for both oral and general health biomarkers' detection gains increasing attention from scientists and clinicians since saliva presents an easily accessible and sophisticated diagnostic fluid with a great potential for integration in various microfluidic setups [7]. In recent years, these systems have even exploited microelectronics, biotechnologies, and integration into smartphones to provide portable and miniaturized analytical devices. Despite the rapid development of microfluidic systems and their applications in many disciplines, a very small number of these systems are commercially and clinically available [8, 9, 10]. Of particular importance are microfluidic systems that allow simultaneous detection of multiple biomarkers in real time. Dental caries is a complex, multifactorial disease that affects a large proportion of the general population, regardless of age, gender, or ethnicity. It is a disease that is directly de pendent on diet, microorganisms of the oral cavity, and defense mechanisms that contribute to oral homeostasis. Saliva pH is an important factor in caries' prevention due to its role in the maintenance of saturation with regard to hydroxyapatite. This protective effect of saliva or intrinsic remineralization potential strongly depends on the chemical composition of saliva, since, at physiological pH, saliva is supersaturated with phosphoprotein stabilized calcium and phosphate ions in the form of Ca2+ and PO4\({}^{3-}\)[11]. When the saliva pH or the plaque pH is below a 'critical value' of about 5.5, the saliva or plaque becomes unsaturated and demineralization processes become predominant. Changes in salivary pH are closely related to the caries' resistance properties of saliva and are, therefore, used to evaluate the intensity of tooth decay. It has been reported that the normal pH of saliva is between 6 and 7, suggesting that it is slightly acidic with the pH in the salivary flow range from 5.3 to 7.8 [12]. Data regarding O2 content in human saliva are extremely rare. It is a broadly accepted fact that low O2 concentration yields to cell apoptosis and tissue damage. Two reports regarding O2 concentration in saliva report the range between 2 and 10 uM [13]. A few earlier studies have shown that total CO2 in saliva increases with flow rate [14; 15]. It has been described that the content may be less than 1 mM in unstimulated saliva and may also approach 60 mM in highly stimulated salivation. Intraoral acid-base relationships and the role of gases in this equilibrium have long been suspected of contributing to dental caries' risk, but the results in this field are contradictory [16]. Numerous agents have been described in the literature as having anticariogenic properties. Xylitol [17] is a non-fermentable sugar alcohol that has the potential to reduce Streptococcus mutans' levels by interfering with bacterial metabolic cycle by a self-destroying mechanism involving dephosphorylation of xylitol-5-phosphate [13]. Anticariogenic effects of xylitol may stem from several mechanisms [18].