A universal approach for synthesis of copper nanoclusters templated by G-rich oligonucleotide sequences and their applications in sensing

Herein, five common G4 sequences have been selected, including three different length of telomere DNA, hemin aptamer, and thrombin aptamer, to synthesize Cu nanoclusters (Cu NCs) in-situ. All G4s are proper templates for Cu NCs with low temperature treatment. The particles (G4-Cu NCs) smaller than 3 nm in diameter were obtained and showed light green fluorescence. This is the first report of metal clusters templated by G4s in-situ. As proof of the concept, hemin and alkaline phosphatase (ALP) were used as the targets to test whether the system can monitor the interaction between G4s and its substrate. The results suggest that G4-Cu NCs can indicate the behavior of G4 and its interaction with hemin, and sensing ALP is achieved with the aid of ATP. The linear ranges of hemin and ALP are 300–4000 nM and 10–500 U/L, respectively, and the corresponding limits of detection as low as 97 nM for hemin and 2.8 U/L for ALP. Moreover, this present system has been successfully applied for the detection of ALP in human serum samples with satisfactory recoveries. This synthesis approach is universal, and it can be easily extended to evaluating the formation of G4, or monitoring the interaction between G4 and its substrate, or selective targeting individual G4, or sensitive detection of other important biomarkers by changing template G4 sequence.