Aptamer-based sensors for fluid biopsies of protein disease markers

Fluid biopsy technology, characterized by its minimally invasive nature, speed, and continuity, has become a rapidly advancing and widely applied real-time diagnostic technique. Among various biomarkers, proteins represent the most abundant class of disease indicators. The sensitive and accurate detection of protein markers in bodily fluids is significantly influenced by the control exerted by recognition ligands. Aptamers, which are structurally dynamic functional oligonucleotides, exhibit high affinity, specific recognition of targets, and notable characteristics of high editability and modularity. These features make aptamer universal "recognition-capture" components, contribute to a significant leap in their applications within the biosensor domain. In this context, we provide a comprehensive review of the extensive application of aptamer-based biosensors in fluid biopsy. We systematically compile the characteristics and construction strategies of aptamer-based biosensors tailored for fluid biopsy, including aptamer sequences, affinity (K_D), fluid background, sensing technologies, sensor construction strategies, incubation time, detection performance, and influencing factors. Furthermore, a comparative analysis of their advantages and disadvantages was conducted. In conclusion, we delineate and deliberate on prospective research trajectories and challenges that lie ahead in the realm of aptamer-based biosensors for fluid biopsy.