Synthesis of Fluorescent Titanium Nanoclusters at ambient temperature for highly sensitive and selective detection of Creatine Kinase MM in myocardial infarction

Abstract

Fluorescent-based biosensing in Photoluminescence nanomaterials has emerged as a new sensing platform commonly used for disease diagnosis. However, the synthesis of Titanium nanoclusters is highly challenging since Titanium is easily oxidized into TiO₂ at ambient temperature. To overcome this problem, we used an acidic medium and simple and robust protocol to synthesize the Titanium nanoclusters of 3-4 nm diameter, which could report the first fluorescent Titanium nanoclusters. New approaches for the novel synthesis of TiNCs can be used for rapid sensing of myocardial infarction (cardiac arrest). In converting creatine to phosphocreatine, CK-MM activates the reaction to convert ATP to ADP, thereby releasing the phosphate groups. Titanium nanoclusters bind strongly to the phosphate group and then quench the Fluorescence. Thus, this phenomenon can be further applied for quantification approaches. The quenching of fluorescence intensity with CK-MM concentration is linear with R² = 0.9829. The current approach can be applied for CK-MM sensing for a wide concentration range (0.625 U/L - 10 U/L). The detection limit was 0.2513 ng/ml in aqueous medium and 0.3465 ng/ml in human serum with high sensitivity when compared with the previous reported methods. Also, this is the first fluorescent-based sensing method to detect CK- MM. The fluorescent TiNCs is a novel platform to be widely applied for the phosphopeptide and phosphoprotein analysis due to the strong and covalent bondings between Ti with P atoms in the near future in medicine, biomedicine, and biological fields.

Keywords: Creatine kinase-MM; Fluorescence; Myocardial infarction; Phosphoprotein; Titanium nanoclusters.