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

Abstract

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.

Keywords: aptamer; biomarker; biosensor; electrochemistry; nanotechnology; sepsis.

Figure 1

A conceptual overview and diagnosis of systemic inflammatory response syndrome (SIRS), infection, sepsis, severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS), and death. (a) Complex interrelationships; (b) progression from SIRS to death.

Figure 2

Electrochemical signal processing in biosensor-based sepsis detection. The biosensing step (1) involves target recognition through aptamer–analyte binding on modified gold nanoparticles (AuNPs), generating a recognition signal. The transducer unit (2) converts this biological interaction into an electrochemical signal, which is then processed and interpreted (3) using various techniques, such as cyclic voltammetry (CV), differential pulse voltammetry (DPV), chronoamperometry (CA), linear sweep voltammetry (LSV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS).

Figure 3

Schematic illustrations of electrochemical aptamer-based biosensors for sepsis biomarker detection. (a) CNT-FET aptasensor for CRP detection with a buried-gate transistor; (b) OECT aptasensor functionalized with AuNPs for IL-6 quantification; (c) EIS aptasensor platform in human serum for IL-6; (d) MXene-GO composite FET aptasensor for E. coli and LPS detection; (e) dual-recognition aptasensor combining aptamers and antibodies on AuNPs for PCT detection; (f) PBA-graphene electrochemical platform for LPS cis-diol binding.

Figure 4

Overview of aptamer–electrochemical biosensors for sepsis diagnostics. This schematic highlights key target biomarkers, including CRP, interleukins (IL-6 and TNF-α), PCT, and LPSs, alongside the unique performance advantages of aptamer-integrated electrochemical platforms, such as low detection limits and rapid response. These attributes support their potential for translation into clinical applications, particularly through multiplexing capabilities and integration with portable diagnostic tools.