Analytical device miniaturization for the detection of circulating biomarkers

Diverse (sub)cellular materials are secreted by cells into the systemic circulation at different stages of disease progression. These circulating biomarkers include whole cells, such as circulating tumour cells, subcellular extracellular vesicles and cell-free factors such as DNA, RNA and proteins. The biophysical and biomolecular state of circulating biomarkers carry a rich repertoire of molecular information that can be captured in the form of liquid biopsies for disease detection and monitoring. In this Review, we discuss miniaturized platforms that allow the minimally invasive and rapid detection and analysis of circulating biomarkers, accounting for their differences in size, concentration and molecular composition. We examine differently scaled materials and devices that can enrich, measure and analyse specific circulating biomarkers, outlining their distinct detection challenges. Finally, we highlight emerging opportunities in biomarker and device integration and provide key future milestones for their clinical translation. Circulating biomarkers can be detected and analysed in the form of liquid biopsies to improve disease diagnosis and monitoring. This Review discusses the integration of specific assay designs in miniaturized device platforms for the detection of circulating biomarkers, including whole cells, extracellular vesicles and cell-free factors.