Electrochemical sensor for glutathione detection based on mercury ion triggered hybridization chain reaction signal amplification

In this work, we design a new simple and highly sensitive strategy for electrochemical detection of glutathione (GSH) via mercury ion (Hg2+) triggered hybridization chain reaction (HCR) signal amplification. It is observed that in the absence of GSH, a specific thymine–Hg2+–thymine (T–Hg2+–T) coordination can fold into hairpin structures. While in the presence of GSH, it thus can be chelated with Hg2+, resulting in Hg2+ released from the T–Hg2+–T hairpin complex which then forms into ssDNA structure to further hybridize with the surface-immobilized capture DNA probe on the gold electrode with a sticky tail left. The presence of two hairpin helper probes through HCR leads to the formation of extended dsDNA superstructure on the electrode surface, which therefore causes the intercalation of numerous electroactive species ([Ru(NH3)6]3+) into the dsDNA grooves, followed by a significantly amplified signal output whose intensity is related to the concentration of the GSH. Taking advantage of merits of enzyme-free amplification power of the HCR, the inherent high sensitivity of the electrochemical technique, and label-free detection which utilizes an electroactive species as a signaling molecule that binds to the anionic phosphate backbone of DNA strands via electrostatic force, not only does the proposed strategy enable sensitive detection of GSH, but show high selectivity against other amino acid, making our method a simple and sensitive addition to the amplified GSH detection.