Microfluidics for Blood Disorders and Hematological Disease Monitoring and Modeling

Blood disorders encompass a wide range of diseases including anemia, hemophilia, thrombotic disorders, platelet dysfunction, and hematological cancers, making blood disorders a major global health concern. These conditions can impair processes vital to human physiology including oxygenation, coagulation, and immune defense. Hematologic malignancies, both chronic and acute, require timely diagnosis and ongoing disease monitoring for effective clinical management. Microfluidic technologies have emerged as promising alternatives to benchtop techniques for diagnosing and monitoring hematological disorders. For example, microfluidic assays can be used for the isolation and characterization of liquid biopsy markers such as rare cells, extracellular vesicles, and cell-free molecules to support disease management in a minimally invasive manner while the process automation afforded by microfluidics decentralizes healthcare, making it more accessible. Advances in lab-on-a-chip technologies, including large-scale fabrication methods and novel design strategies, will provide tools for the clinical validation of biomarkers and the translation of these technologies from the laboratory bench to the patient bedside. In this review, we will show that microfluidic devices enable disease monitoring via high-throughput analysis of liquid biopsy samples for the detection of rare disease-specific biomarkers found in blood, plasma, urine, etc., providing an alternative to standard benchtop testing using specimens secured via invasive bone marrow procedures, typically used for managing blood-based diseases. A key advantage of microfluidics is their ability to manipulate blood components at scales that closely mimic the body's microvascular environment. Not surprisingly, microfluidic vascular models have been developed to replicate physiological rheology enabling quantitative assessment of blood cell deformability, aggregation, or clot formation. We provide a critical perspective on the use of the microfluidic "organ-on-chip" designed for blood disorders' modeling and employed to recapitulate the blood cancer microenvironment. A summary of advances in microfluidic strategies for detection, diagnosis, drug screening, and mechanistic investigations of blood disorders, and future directions for precision testing, will be presented.