Advanced Multipurpose Spectroscopic Nanobio-Device for Concurrent Lab-on-a-Chip Label-Free Separation and Detection of Extracellular Vesicles as Key-Biomarkers for Point-of-Care Cardiovascular Disease Diagnostics.

Abstract

The global aging population presents a major public health challenge, with cardiovascular diseases (CVDs) remaining the leading cause of death worldwide. Often asymptomatic in early-stages, CVDs are frequently undiagnosed until critical events like myocardial infarction or stroke occur. To address this gap, an advanced integrated multipurpose spectroscopic lab-on-a-chip bionano-device has been developed for early CVD detection through extracellular vesicle (EV). EVs, which reflect the molecular state of their originating cells, are separated and analyzed using the combined Raman spectroscopy's molecular specificity with AI-driven classification from clinical CVD biofluids. AIMSpec-LoC unprecedently achieves rapid, label-free, size-based separation of EV subtypes, including small, mid and large EVs from biofluids, whilst preserving EV integrity and eliminating extensive preprocessing. The device enables real-time, multiplexed molecular profiling of EV cargo, identifying CVD-specific biomarkers with sensitivity and specificity >96% and linking these to CVD progression, achieving >97% accuracy in identifying disease-specific molecular fingerprints. This bionanotechnological device generates quantitative barcodes to support prognostic modeling and therapeutic evaluation, providing clinicians with actionable insights for timely-diagnosis and personalized treatment. AIMSpec-LoC platform offers a transformative solution for point-of-care CVD diagnostics, addressing critical unmet needs in cardiovascular medicine, enhancing clinical decision-making, improving patient health and reducing the global burden of CVDs.