Furthermore, recent clinical and epidemiological studies have demonstrated the association between inflammation and cardiovascular diseases [21]. event taking place at the gate electrode, functionalized with a self-assembled monolayer (SAM) of highly densely packed capturing anti-CRP proteins. Thanks to the SAM, the biosensing platform herein proposed is endowed with ultra-high sensitivity, along with an extremely high selectivity, assessed by measuring the dose curves of CRP interacting with a bovine serum albumin-functionalized gate. Moreover, the biosensing platform is compatible with low-cost fabrication techniques and applicable to the ultra-sensitive detection of a plethora of clinically relevant biomarkers. PKI-587 ( Gedatolisib ) Therefore, the EGOTFT device herein proposed, being able to operate in physiologically relevant fluids such as saliva, will set the PKI-587 ( Gedatolisib ) ground to a major revolution in biosensing applications for early clinical detection. Keywords: Electrolyte-gated organic thin-film transistor, Single molecule, Wide-field transistors, Analytical sensors, CRP detection, Saliva Introduction The analysis of human biofluids, such as the blood, urine, saliva, tears, and sweat, yields useful clinical information for the evaluation and monitoring of health and disease states [1]. Lab-on-a-chip systems able to quantify clinically relevant biomarkers in physiological fluids and compatible with point-of-care testing have shown terrific advancements in the last decade, foreseeing a revolution in early clinical diagnostics [2C6]. In this perspective, accurate, compact, easy to use, and possibly non-invasive diagnostics represents the ideal candidate for point-of-care testing, especially for geriatric and pediatric patients and for mass screening, where minimally invasive collection of diagnostic material is a pivotal aspect [7]. Blood products, i.e., the serum and plasma, have been so far the most widespread and conventional biofluids for clinical testing. In fact, blood flows and diffuses through all tissues and organs, collecting by-product of many pathological states. Therefore, the concentrations of specific relevant biomarkers in plasma or serum have been associated with ongoing disease states, leading to a plethora of fundamental clinical applications [8]. However, in the last decade, saliva has Igf1 been promoted as a noninvasive alternative to blood as diagnostic fluid. Saliva represents a very complex matrix, containing both secretion from salivary glands and non-salivary components, such as metabolites and signal molecules accompanying remote processes [9]. In fact most metabolites, cytokines, proteins, and hormones move by passive filtration into saliva from bloodstream. It has been recently proven that their levels in saliva reflect their blood concentrations [10]. During the last few years, great efforts have been made worldwide to characterize and compare the protein compositions of salivary PKI-587 ( Gedatolisib ) and blood fluids [11]. Proteomic analyses of saliva have highlighted the presence of over 2000 proteins, approximately 25C30% of which are shared with blood [7]. The significant correspondence in protein content between saliva and plasma suggested that saliva could be suitable as a diagnostic alternative to blood tests. Indeed, the use of saliva as an alternative to blood-based assay offers many advantages. In particular, saliva is readily available from most individuals, can be easily collected, stored, and processed. Moreover, the collection procedure is noninvasive, painless, and cost-effective [12]. However, the diffusion of saliva has clinically relevant biofluid has been hindered so far by the insufficient sensitivity of current analytical methods to detect the lower salivary concentrations of many biomarkers compared to blood products [13]. Therefore, salivary diagnostics applicability requires ultra-highly sensitive biosensing platform, being able to selectively detect a specific biomarker in a complex matrix at physiological concentrations. To the best of PKI-587 ( Gedatolisib ) our knowledge, the present lack of practical detection methodologies represents a major limiting factor, because most current assays do not provide the necessary sensitivity for the detection of biomarkers at the low, but still patho-physiologically relevant, concentrations in saliva [14, 15]. Among the plethora of biomarkers whose quantification in saliva PKI-587 ( Gedatolisib ) could potentially contribute to monitor the onset of many pathological states, C-reactive protein (CRP) has attracted a great deal of attention. In fact, CRP has been known since the 1930s as an acute phase protein of the immunoresponse [16]. CRP is a non-glycosylated protein with a molecular weight of c.a. 115?kDa, constituted by five non-covalently bound, identical, and spherical subunits, each one of about 20C28?kDa [17]. These subunits are held together in a circular structure called pentraxin [18]. The CRP blood level is presently routinely checked because of its relevance as biomarker for systemic inflammation arising from immune system stimulation, such as infection.