Electrolyte-Gated Organic Electrochemical Transistor for Dynamic HMGB1 Detection in Acute Kidney Injury

Early detection and continuous monitoring of acute kidney injury (AKI) are essential for preventing progression to chronic kidney disease (CKD). However, conventional renal biomarkers such as serum creatinine lack sensitivity for deterioration warnings. High mobility group box 1 (HMGB1), a pivotal damage-associated molecular pattern protein, has emerged as a dynamic indicator of renal injury and repair. Here, we report an electrolyte-gated organic electrochemical transistor (OECT) biosensing platform functionalized with a high-affinity DNA aptamer for the selective and rapid detection of HMGB1. The aptamer-modified gate electrode enables precise molecular recognition, while mixed ionic-electronic transport within the active channel facilitates efficient signal transduction. The resulting biosensor exhibits a broad detection range of 5 pM to 50 nM and operates reliably across diverse physiological electrolytes, including phosphate-buffered saline, albumin, and serum. Pulse-driven measurements further enhance the response sensitivity and enable rapid signal acquisition within seconds. Validation in a mouse model of ischemic AKI reveals that the electrical responses of the biosensor correlate quantitatively with HMGB1 level fluctuations during the AKI-to-CKD transition. This study establishes a robust, OECT-based sensing strategy for rapid HMGB1 monitoring, offering a promising tool for the early diagnosis and prognosis assessment of kidney injury.