Metabolomics-guided molecularly imprinted electrochemical sensor for noninvasive embryo quality assessment

Accurate assessment of embryo quality remains a major challenge in the context of in vitro fertilization (IVF), since it significantly affects implantation success and clinical outcomes. Although metabolomics profiling of embryo culture medium (CM) holds promise for identifying biomarkers for embryo viability, no widely accepted indicators have yet been established. In this study, methylguanidine, L-valine, and oleic acid were identified as potential metabolic markers associated with embryo quality through semi-targeted metabolomics analysis of day 3 (D3) embryo CM. To enable sensitive and selective detection, a three-functional-module electrochemical sensing platform (TMEP) based on molecular imprinting was developed. An in situ grown RGO/Ni₃(HITP)₂ conductive metal–organic framework (MOF) composite was employed as the electrode material, which enhanced the conductivity and electrochemical performance of the sensing interface. The TMEP demonstrated high sensitivity, achieving detection limits of 2.3, 1.8 and 3.2 pM for methylguanidine, L-valine, and oleic acid, respectively. In addition, satisfactory recoveries (97.9%–104.8%, 95.4%–105.2%, and 97.2%–104.0%, respectively) and low relative standard deviations (RSDs <3.88%) confirmed its excellent reproducibility. Notably, the platform was successfully validated using clinical embryo CM samples, demonstrating its practical applicability for non-invasive embryo quality evaluation in IVF.