Point-of-care detection for respiratory diseases: From samples and biomarkers to principles and applications

Early screening can significantly reduce the severe morbidity and mortality of respiratory diseases and alleviate the burden on public healthcare systems. Point-of-care (POC) devices refer to portable instruments that meet the REASSURED criteria and can be conveniently used near the patient without professional laboratory conditions. POC devices played an important role in patient initiated early diagnosis during the COVID-19 pandemic, demonstrating great potential. From a macro-to-micro perspective, this review first comprehensively introduces clinically relevant sample types, including blood, respiratory tract and oral samples, and exhaled breath, along with the clinical significance of corresponding biomarkers (nucleic acids, proteins, gaseous molecules, extracellular vesicles, circulating tumor cells, and pathogen particles) and pre-processing methods. Subsequently, it summarizes the test principles and promising bioreceptors including base pairing-based systems (PCR, isothermal amplification, CRISPR/Cas), antibodies and antibody mimetics, and other affinity-based recognition elements, and innovatively presents portable integration platforms of biosensors from the perspective of bioreceptor compatibility. It then evaluates the application performance of transducers and corresponding optical or electrochemical portable detection devices, including SERS, e-nose, nanopore sensors, and portable GC-MS. Finally, the latest applications of computer technology and artificial intelligence tools in POC detection for respiratory diseases, spanning device design, bioreceptor screening, biomarker discovery, and diagnostic data processing, are presented by functional category. This review aims to provide a reference for the research and application of multiplex biomarker/sample/disease POC testing in respiratory diseases, and to offer perspectives on future directions for technological innovation, intelligentization, and commercial translation.