Preeclampsia Diagnosis Using β‐Hairpin Peptide for ELABELA Detection

ABSTRACT 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.