Microfluidic assessment of PO₂-regulated RBC capillary velocity in ME/CFS Open Access

1. PO₂-regulated RBC capillary velocity is impaired in ME/CFS.

2. RBC velocity response to PO₂ is a unique characteristic in ME/CFS.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology that affects multiple organ systems. Although there is no established treatment or diagnostic test for ME/CFS yet, studies have consistently demonstrated impaired cerebral blood flow (CBF) and blood flow regulation in ME/CFS. In this study, we measured red blood cell (RBC) velocity in microfluidic capillaries at varied oxygen tensions (PO₂) and showed that, compared to RBCs from heathy controls, RBCs from ME/CFS exhibit compromised capillary velocity in response to reduced PO₂. To examine whether such PO₂-regulated RBC capillary velocity could be used to assess or diagnose ME/CFS, we conducted receiver operator characteristic (ROC) analysis and used machine learning (ML) to analyze various features of PO₂-regulated RBC capillary velocity. We found that velocity slope-based classifiers were highly accurate, sensitive and specific (i.e., 77.8%, 76% and 90% respectively) in ME/CFS classification. Furthermore, we demonstrated this RBC-based microfluidic approach can be used to evaluate potential drugs (i.e., salmeterol xinafoate and xanomeline) for improving RBC capillary velocity in ME/CFS. These findings highlight previously unrecognized roles of RBCs in the pathophysiology of ME/CFS and suggest a potential RBC-based test for ME/CFS diagnosis.