Ratiometric electrochemical biosensor based on Cu(II) modified covalent organic framework for the ultra-sensitive and specific detection of glutathione

As a vital biological polypeptide molecule, glutathione (GSH) is involved in the regulation of various life activities. Accurate and sensitive detection of GSH in human body is of great significance for the preliminary diagnosis of related diseases. In this research, Cu(II) modified TADH COF, which has been prepared by Cu2+ post-synthesis modification of the COF obtained through a condensation reaction of 1,3,5-(4-aminophenyl) benzene (TAPB) and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde (DHTP), and methylene blue (MB) molecules are combined to construct a ratiometric electrochemical sensor for achieving specific and ultra-sensitive detection of GSH. As a stable and active covalent organic framework material, TADH COF possesses the special O(–OH) and N(CN) binding sites, which can load and coordinate with Cu2+ effectively. The obtained Cu(II)-TADH COF serves as a sensitive electrode material for sensing GSH due to “extrusion effect” caused CuCl solid-state electrochemical signal degeneration by the specific binding of Cu and GSH while MB provides a stable electrical signal in the electrochemical sensing process as an internal reference for eliminating errors and making the detection results more accurate. The constructed electrochemical sensing platform Cu(II)-TADH COF/MB/GCE exhibited an ultrahigh sensitivity with a limit of detection (LOD) of 0.0093 nM (S/N = 3), wide linear range of 0.05 nM–40 μM and high accuracy. For the detection of GSH in real samples including human blood, serum and urine samples, the sensor also showed excellent sensing performance. This is the first research on ratiometric electrochemical sensing platform for the ultra-sensitive detection of glutathione based on covalent organic frameworks, which provides an original and novel strategy for the electrochemical detection of GSH with COF materials.