3D Matrix-Arranged AuAg Nanoclusters As Electrochemiluminescence Emitters for Click Chemistry-Driven Signal Switch Bioanalysis.

We hereby described an electrochemiluminescence (ECL) biosensor for glutathione (GSH) based on a 3D DNA matrix with ordered binding sites and cavity structure that self-assembled from tetrahedral DNA blocks (TDBs). First, the alkyne-labeled TDBs were employed to build an alkyne-rich 3D matrix (C≡C-3DM) on the electrode surface. Then, the GSH-induced click chemistry was triggered as a signal switch to introduce the large amounts of N3-DNA decorated AuAg nanoclusters (N3-AuAg NCs) into C≡C-3DM for signal output. In particular, the presence of GSH could induce the formation of GSH-Cu(I) complex by the redox reaction between GSH and Cu(II), which could act as an initiator to link the N3-AuAg NCs with C≡C-3DM according to the Huisgen 1,3-dipolar cycloaddition reaction. By this way, numerous N3-AuAg NCs were orderly bonded to the 3D matrix to effectively reduce their agglomeration and inner filter effect, achieving a remarkable ECL enhancement. As a result, the proposed GSH biosensor showed a wide linear range from 5 to 200 μM with a low detection limit of 0.90 μM. In general, this work provided a rapid, highly efficient, and convenient signal amplification for small-molecule detection and broadened the application of TDBs in biosensing.