Electrochemical Aptamer-Based Biosensors for Sepsis Diagnosis: Recent Advances, Challenges, and Future Perspectives (2020–2025)

Sepsis remains a global health emergency, demanding timely and accurate diagnostics to reduce morbidity and mortality. This review critically assesses the recent progress (2020–2025) in the development of electrochemical aptamer-based biosensors for sepsis detection. These biosensors combine aptamers’ high specificity and modifiability with the sensitivity and miniaturization potential of electrochemical platforms. The analysis highlights notable advances in detecting key sepsis biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (e.g., interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), lipopolysaccharides (LPSs), and microRNAs using diverse sensor configurations, including a field-effect transistor (FET), impedance spectroscopy, voltammetry, and hybrid nanomaterial-based systems. A comparative evaluation reveals promising analytical performance in terms of the limit of detection (LOD), rapid response time, and point-of-care (POC) potential. However, critical limitations remain, including variability in validation protocols, limited testing in real clinical matrices, and challenges in achieving multiplexed detection. This review underscores translational barriers and recommends future directions focused on clinical validation, integration with portable diagnostics, and interdisciplinary collaboration. By consolidating current developments and gaps, this work provides a foundation for guiding next-generation biosensor innovations aimed at effective sepsis diagnosis and monitoring.