Novel molecularly imprinted polymer (MIP) multiple sensors for endogenous redox couples determination and their applications in lung cancer diagnosis.

Abstract

Multiplex electrochemical sensors for amperometric detection of glutathione disulfide (GSSG), glutathione (GSH), cysteine (Cys), cystine (Cyss), β-nicotinamide adenine dinucleotide phosphate (NADP+) and coenzyme II reduced tetrasodium salt (NADPH) were developed, in which analysis of Cyss, NADP+ and NADPH are the first report using this sensing system. Specificity of these sensors were ensured by a layer of molecularly imprinted polymer (MIP) which was electropolymerized in situ with the analytes as template. All the sensors were tested with standard buffers and mouse blood samples, showing satisfactory performance towards the corresponding analytes. Dynamic concentration for the six analytes was in the range of 10-11-10-8 mol/L with the detection limit down to 20 pmol/L. In addition, artificially synthesized MIP film on the electrodes allowed for good selectivity and stability. Real blood sample measurement proved that the sensors owned decent accuracy with recovery value ranging from 92%~112%. More importantly, blood samples from lung cancer patients and healthy donors were assayed by using the proposed sensors. Redox potentials (Ehc) were calculated based on the contents of these endogenic substances, which were utilized to reflect the health status of human body and help diagnose lung cancer. The levels of GSH, NADPH and the absolute value of Ehc(GSH/GSSG) in patients with lung cancer are significantly lower (P\u202f<\u202f0.01) than those in healthy people, while the contents of GSSG (P\u202f<\u202f0.01) are higher. The blood test results suggested that the content of GSH, NADPH, NADP+ and Ehc(GSH/GSSG) might serve as biomarkers for lung cancer prediagnosis. These novel sensors for liquid biospy of cancer have cost-benefit and scalability advantage over current techniques, potentially enabling broader clinical access and efficient population screening.