Paper-assisted matrix mitigation and preconcentration for electrochemical detection of 8-oxoguanine in serum.

8-Oxoguanine (8-oxoG) is one of the most biologically relevant oxidative lesions of nucleic acids and is widely investigated as a biomarker of oxidative stress and oxidative nucleic acid damage. Its reliable monitoring in biological matrices is important; however, conventional chromatographic and mass spectrometric methods require expensive instrumentation, trained personnel, and laborious sample preparation. In this work, we report a hybrid electrochemical strategy based on carbon black-modified printed sensors coupled with a wax-patterned paper disk for the rapid determination and passive preconcentration of free 8-oxoguanine in serum. In the proposed configuration, the printed electrochemical sensor acts as the transducing element, while the paper disk serves as a functional sample-treatment interface that modulates sample delivery, partially mitigates serum-related signal suppression, and enables passive analyte preconcentration ahead of voltammetric detection. The platform was systematically optimized by evaluating the carbon black modification, the role of the paper disk, and the differential pulse voltammetry parameters for 8-oxoguanine oxidation. Analytical performance was assessed in buffer and spiked human serum. Following five-fold preconcentration, the paper-assisted configuration achieved a limit of detection of 0.3 μM and a limit of quantification of 1 μM in serum, while partially counteracting matrix-related signal suppression. The quantitative performance of the platform was preliminarily evaluated through spiked-sample analysis and comparison with LC-MS/MS measurements. Overall, this strategy demonstrates that coupling printed electrochemical transduction with the paper disk can improve sensitivity and compatibility with serum analysis, providing a simple and cost-effective platform for free 8-oxoguanine determination in biological matrices.