Preeclampsia Diagnosis Using β‐Hairpin Peptide for ELABELA Detection

Preeclampsia (PE) poses risks to mothers and infants, especially in low-resource settings. Diagnosis of PE is difficult due to nonspecific symptoms and limited biomarker screening. ELABELA, a circulating peptide hormone and endogenous ligand of the apelin receptor (APJ), has emerged as a promising biomarker for earlier detection of PE, alone or in combination with other biomarkers. Here, we present β-hairpin protein epitope mimetics (BH-PEMs) as a tool for ELABELA detection. Employing an epitope mimetics approach, OP27 from a BH-PEM peptide library emerged as a high-affinity candidate for ELABELA following rational design and screening of a focused peptide library. Experimental assays verified the OP27-ELABELA complex's stability and binding affinity. We successfully detected ELABELA in clinical donor serum samples using the OP27-ELABELA complex-based electrochemical method integrated with electrochemical impedance spectroscopy (EIS), enabling sensitive detection in a complex biological matrix. Our findings establish a proof-of-concept biomarker-driven electrochemical detection strategy for PE, supporting the development of simplified electrochemical diagnostic approaches while highlighting the broader applicability of BH-PEM probes in biomarker detection. The BH-PEM probe demonstrates feasibility for biomarker-driven PE detection and warrants further validation in expanded clinical cohorts, thereby contributing to improved maternal risk assessment and mitigation of health risks for mothers and infants.