Significance: Carbon dots (CDs) have attracted a host of research interest in recent years mainly due to their unique photoluminescence (PL) properties that make them applicable in various biomedical areas, such as imaging and image-guided therapy. However, the real mechanism underneath the PL is a subject of wide controversy and can be investigated from various angles. Aim: Our work investigates the effect of the isomeric nitrogen position as the precursor in the synthesis of CDs by shedding light on their photophysical properties on the single particles and ensemble level. Approach: To this end, we adopted five isomers of diaminopyridine (DAP) and urea as the precursors and obtained CDs during a hydrothermal process. The various photophysical properties were further investigated in depth by mass spectroscopy. CD molecular frontier orbital analyses aided us in justifying the fluorescence emission profile on the bulk level as well as the charge transfer processes. As a result of the varying fluorescent responses, we indicate that these particles can be utilized for machine learning (ML)-driven sensitive detection of oral microbiota. The sensing results were further supported by density functional theoretical calculations and docking studies. Results: The generating isomers have a significant effect on the overall photophysical properties at the bulk/ensembled level. On the single-particle level, although some of the photophysical properties such as average intensity remained the same, the overall differences in brightness, photo-blinking frequency, and bleaching time between the five samples were conceived. The various photophysical properties could be explained based on the different chromophores formed during the synthesis. Overall, an array of CDs was demonstrated herein to achieve similar to 100% separation efficacy in segregating a mixed oral microbiome culture in a rapid (< 0.5 h), high-throughput manner with superior accuracy. Conclusions: We have indicated that the PL properties of CDs can be regulated by the precursors' isomeric position of nitrogen. We emancipated this difference in a rapid method relying on ML algorithms to segregate the dental bacterial species as biosensors.

The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.

Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO2) (∼1-2 nm) nanoparticles. The minute-made synthesis of these nanoparticles is accomplished through a simple reduction reaction. These nanoparticles were incubated with probiotic bacteria with potential health benefits and were non-specifically taken up due to their small size. Subsequently, the bacteria were lyophilized and packed into a capsule to be administered orally as the radiopaque contrast agents for delineating the GI features. These nano-bio-hybrid entities could successfully be utilized as contrast agents in vivo in the conventional and multispectral computed tomography (CT). We demonstrated in 'color' the accumulated nanoparticles using advanced detectors of the photon counting CT. The enhanced nano-bio-interfacing capability achieved here can circumvent traditional nanoparticle solubility and delivery problems while offering a patient friendly approach for GI imaging to replace the currently practiced barium meal.